Predicting post-treatment survival in cancer patients with microRNAs

ABSTRACT

This invention provides a method for predicting the post-treatment survival prospect of a cancer patient based on the expression level(s) of microRNAs hsa-miR137, hsa-miR372, hsa-miR182*, hsa-miR221, and hsa-let-7a in that cancer patient.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application No. 60/910,993, filed on Apr. 10, 2007, the contents of which are hereby incorporated by reference in its entirety.

BACKGROUND

Lung cancer, predominantly non-small-cell lung cancer (NSCLC), is the most common cause of cancer deaths worldwide. See Jemal et al., CA Cancer J. Clin. 56:106-130 (2006). Early-stage NSCLC patients show a relapse rate of 40% within 5 years after treatment; it is suggested that the disease stage might be a factor associated with clinical outcomes. See Miller, Am. J. Respir. Cell Mol. Biol. 33: 216-223 (2005). However, this factor alone is inadequate to predict such outcomes.

It has been suggested that gene expression profiling, in particular, microRNA profiling, is useful in both cancer diagnosis and prognosis. See Endoh et al., J. Clin. Oncol. 22:811-819 (2004); and Potti et al., N. Engl. J. Med. 355:570-580 (2006). For example, the expression patterns of certain microRNAs are found to be more accurate than the expression patterns of protein-coding genes in determining cancer subtypes. See Calin et al., Nat. Rev. Cancer 6:857-866 (2006); and Volinia et al., Proc. Natl. Acad. Sci. U.S.A. 103:2257-2261 (2006).

MicroRNAs are small non-protein-coding RNAs that regulate the expression of hundreds of genes post-transcriptionally via RNA interference, thereby controlling a broad range of biopathways, e.g., cell proliferation, differentiation, and apoptosis. See Calin et al., 2006. Certain microRNA signatures, i.e., one or more microRNAs that display particular expression patterns in a group of patients, were reported to be associated with clinical outcomes of chronic lymphocytic leukemia, lung adenocarcinoma, breast, pancreas and cancers. See Calin et al., 2006. Identifying new microRNA signatures is of great interest, as they would be useful tools in predicting clinical outcomes of various cancers, in particular, NSCLC.

SUMMARY

This invention is based on the observation that the expression levels of certain microRNAs, such as hsa-miR137, hsa-miRNA372, hsa-miR182*, hsa-miR221 and hsa-let-7a, correlate with the post-treatment survival prospect of a cancer patient.

In one aspect, this invention provides a method for predicting post-treatment survival prospect of a cancer patient by determining a normalized threshold cycle value (−dCt) based on the expression level of hsa-miR137, hsa-miR372, hsa-miR182*, hsa-miR221, or hsa-let-7a. The patient is determined to have a fair prospect of post-treatment survival if the −dCt value of hsa-miR137, hsa-miR182*, and hsa-miR372 is equal to or lower than −8.22, −7.83, and −11.25, respectively, or if the −dCt value of hsa-miR221 and hsa-let-7a is equal to or higher than −0.57 and 2.21, respectively.

In another aspect, the post-treatment survival prospect of a cancer patient can be predicted based on the expression levels of four of the microRNAs selected from hsa-miR137, hsa-miR372, hsa-miR182*, hsa-miR221 and hsa-let-7a. More specifically,

1. When the expression levels of hsa-miR372, hsa-miR182*, hsa-miR221 and hsa-let-7a are investigated, a risk score is calculated as follows: (0.31×expression level of hsa-miR372)+(0.28×expression level of hsa-miR182*)+(−0.13×expression level of hsa-miR221)+(−0.14×expression level of hsa-let-7a). A risk score equal to or lower than −5.90 indicates that the patient has a fair prospect for post-treatment survival.

2. When the expression levels of hsa-miR137, hsa-miR182*, hsa-miR221 and hsa-let-7a are investigated, a risk score is calculated as follows: (0.15×expression level of hsa-miR137)+(0.28×expression level of hsa-miR182*)+(−0.13×expression level of hsa-miR221)+(−0.14×expression level of hsa-let-7a). A risk score equal to or lower than −3.71 indicates that the patient has a fair prospect for post-treatment survival.

3. When the expression levels of hsa-miR137, hsa-miR372, hsa-miR221 and hsa-let-7a are investigated, a risk score is calculated as follows: (0.15×expression level of hsa-miR137)+(0.31×expression level of hsa-miR372)+(−0.13×expression level of hsa-miR221)+(−0.14×expression level of hsa-let-7a). A risk score equal to or lower than −4.87 indicates that the patient has a fair prospect for post-treatment survival.

4. When the expression levels of hsa-miR137, hsa-miR182*, hsa-miR372 and hsa-let-7a are investigated, a risk score is calculated as follows: (0.15×expression level of hsa-miR137)+(0.28×expression level of hsa-miR182*)+(0.31×expression level of hsa-miR372)+(−0.14×expression level of hsa-let-7a). A risk score equal to or lower than −7.02 indicates that the patient has a fair prospect for post-treatment survival.

5. When the expression levels of hsa-miR137, hsa-miR182*, hsa-miR221 and hsa-miR372 are investigated, a risk score is calculated as follows: (0.15×expression level of hsa-miR137)+(0.28×expression level of hsa-miR182*)+(−0.13×expression level of hsa-miR221)+(0.31×expression level of hsa-miR372). A risk score equal to or lower than −6.86 indicates that the patient has a fair prospect for post-treatment survival.

In yet another aspect, the post-treatment survival prospect of a cancer patient can be predicted based on his or her expression levels of the five microRNAs mentioned above. A risk score is calculated as follows: (0.15×expression level of hsa-miR137)+(0.31×expression of hsa-miR372)+(0.28×expression level of hsa-miR182*)+(−0.13×expression level of hsa-miR221)+(−0.14×expression level of hsa-let-7a). A cancer patient has fair prospect of post-treatment survival if his or her risk score is equal to or lower than −7.1.

In still another aspect, the post-treatment survival prospect can be predicted based on the expression levels of hsa-miR221, hsa-miR372, and hsa-miR137. A risk score is calculated as follows: (0.15×expression level of hsa-miR137)+(0.31×expression of hsa-miR372)+(−0.13×expression level of hsa-miR221). A cancer patient will have a fair prospect of post-treatment survival if the risk score is equal to or lower than −4.7.

A cancer patient having “a fair prospect of post-treatment survival” means that his or her risk of post-treatment death is at least 50% (e.g., 100% or 150%) lower than the average risk of death in patients having the same type of cancer.

Also within the scope of this invention is a kit for detecting the expression of microRNAs. In one example, the kit comprises oligonucleotides capable of detecting the expression of hsa-miR221, hsa-miR372, and hsa-miR137. In another example, it comprises oligonucleotides capable of detecting the expression of at least four microRNAs selected from hsa-miR137, hsa-miR372, hsa-miR182*, hsa-miR221, and hsa-let-7a. The oligonucleotides contained in any of the just-described kits can be immobilized on a supporting member (e.g., a polymer substrate) to form nucleic acid chips.

The cancer patient who has been subjected to treatment (e.g., surgical treatment, chemical treatment, or radio-therapy) has lung cancer (e.g., non-small cell lung cancer of all stages), leukemia, breast cancer, pancreatic cancer, adenocarcinoma, or squamous cell carcinoma, colon cancer or hepatocellular carcinoma.

The details of one or more embodiments of the invention are set forth in the description below. Other features, objects, and advantages of the invention will be apparent from the description and from the claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is a diagram showing a microRNA risk-score analysis of 112 NSCLC patients based on the expression levels of hsa-miR137, hsa-miR372, hsa-miR182*, hsa-miR221, and hsa-let-7a in these patients. Upper panel: MicroRNA risk-score distribution. Middle panel: Patients' death/survival status. Bottom panel: Patients' microRNA expression profiles; the five rows, from bottom to top, refer to hsa-let-7a, hsa-miR221, hsa-miR372, hsa-miR182*, and hsa-miR137, respectively; the columns each represent a patient. The dotted line represents the cut-off line (risk score −7.1) dividing patients into low-risk and high-risk groups.

FIG. 2 is a diagram showing Kaplan-Meier estimates of the overall survival and relapse-free survival of the NSCLC patients in both low-risk and high-risk groups. Panel A shows results obtained from 56 patients in a training dataset; Panel B shows results obtained from 56 patients in a testing dataset; and Panel C shows results obtained from 62 patients in an independent cohort.

FIG. 3 is a diagram showing Kaplan-Meier estimates of the overall survival and relapse-free survival of NSCLC patients in both low-risk and high-risk groups. Panel A shows results obtained from state I NSCLC patients (n=47); Panel B shows results obtained from stage II NSCLC patients (n=28); Panel C shows results obtained from stage III NSCLC patients (n=37); Panel D shows results obtained from adenocarcinoma patients (n=55); and Panel E shows results obtained from squamous cell carcinoma patients (n=50).

DETAILED DESCRIPTION

This application provides a method for predicting a clinical outcome (e.g., the post-treatment survival prospect) of a cancer patient based on the expression patterns of one or more microRNAs that are associated with the clinical outcome.

The one or more microRNAs associated with the outcome can be identified as follows.

A group of post-treatment cancer patients are recruited. These patients, suffering from the same type of cancer, are randomly assigned to a training group and a testing group. The expression levels of a number of microRNAs in cancer tissues/cells (e.g., contained in biopsies, formalin-fixed-paraffin-embedded tissues, or frozen tissues) are determined for the patients in both groups following methods known in the art, e.g., real-time PCR or micro-array analysis. The expression level of each microRNA thus determined is normalized by the expression level of an internal control, such as a small nuclear RNA (e.g., U1, U2, or U6), in the same patient to obtain a normalized expression level.

Normalized expression levels of the microRNAs obtained from the training group are subjected to statistical analysis, e.g., Cox regression analysis, to determine which microRNA(s) is associated with a clinical outcome (e.g., post-treatment survival) of the cancer patients. In one example, hazard ratios obtained from univariate Cox regression analysis are used to identify the microRNA(s) that is associated with death due to recurrence of cancer or any other cause. See Cox, J. Royal Statistical Society Series B 34:187-220 (1972). If the hazard ratio of a microRNA is less than 1, that microRNA is deemed as a protective microRNA, and if the hazard ratio of a microRNA is greater than 1, that microRNA is deemed as a risk microRNA.

Once the microRNAs associated with a clinical outcome (e.g., protective and risk microRNAs) are identified, the correlation between their expression patterns and a clinical outcome can be determined by statistical analysis known in the art. In one example, a risk score is calculated for each patient based on the expression levels of one or more of the protective and/or risk microRNAs, and a relationship between the value of the risk score and a patient's survival period after treatment is then determined. The correlation thus determined is verified in the testing group to confirm that the microRNA expression pattern is truly associated with the clinical outcome of interest. Preferably, this correlation is further validated in an independent cohort including a number of patients having the same type of cancer as those in the training and testing groups.

After verification, and preferably, validation, the identified microRNAs can be used to predict the clinical outcome, based on their expression patterns, in patients having the same type of cancer. For example, one can construct a mathematical formula, taking into consideration both the expression levels of these microRNAs and the significance of the statistical analysis mentioned above. Following this mathematical formula, a risk score is calculated for a patient. The value of the risk score indicates the patient's clinical outcome.

The microRNAs associated with a clinical outcome of a cancer patient can also be used to identify potential targets for cancer treatment. See Czech, N. Engl. J. Med. 354:1194-1195 (2006). Genes targeted by these microRNAs can be identified using microRNA target prediction algorithms, e.g., PicTar, see Krek et al., Nat. Genet. 37:495-500 (2005); TargetScan, see Lewis et al., Cell 115:787-798 (2003); miRNAMap, see Hsu et al., Nucleic Acids Res. 34:D135-139 (2006); miRBase, see Griffiths-Jones et al., Nucleic Acids Res. 34:D140-144 (2006); GenMAPP, see genmapp.org; and Reactome, see reactome.org. These genes and their products are potential targets or agents for cancer therapy.

Without further elaboration, it is believed that the above description has adequately enabled the present invention. The example below shows microRNA signatures that can be used for predicting post-treatment survival prospect in NSCLC patients. This example is to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. All of the publications cited herein are hereby incorporated by reference in their entirety.

Materials and Methods

(a) Patients and Tissue Specimens.

112 consecutive NSCLC patients, all underwent surgical resection, were recruited from the Taichung Veterans General Hospital. These patients were randomly assigned to a training dataset (n=56) and a testing dataset (n=56). In addition, 62 consecutive patients who also underwent surgical resection were recruited from National Taiwan University Hospital. These 62 patients formed an independent cohort. Frozen specimens of lung cancer tissues were obtained from all of the patients recruited for this study. All of the patients are Han Chinese.

(b) MicroRNA Profiling.

MicroRNA expression profiling was performed using ABI PRISM 7900 Real Time PCR System and TaqMan MicroRNA Assays Human Panel-Early Access Kit, which contains primers for determining 157 mature human microRNAs (Applied Biosystems). The cDNA of each microRNAs was first amplified using TaqMan MicroRNA RT reagent and primers specific for that microRNA, and further amplified using TaqMan 2× Universal PCR Master mix. During amplification, a fluorescent dye was incorporated into the cDNA product. The expression level of each microRNA, represented by a threshold cycle (Ct) value, was determined based on the level of the fluorescence generated by the fluorescent dye incorporated into the cDNA product. Ct refers to the fractional number at which the fluorescence passes a fixed threshold. The Ct value of each microRNA was then normalized by that of U6, a common internal control for microRNA quantification assays. See Jiang et al., Nucleic Acids Res. 33:5394-5403 (2005); and Yanaihara et al., Cancer Cell 9:189-198 (2006). More specifically, the normalized Ct value (−dCt) was calculated as follows: −dCt=(Ct_(microRNA)−Ct_(U6)).

(c) Statistical Analysis

Hazard ratios obtained from univariate Cox regression analysis were used to identify the microRNA(s) whose expression levels were associated with patient's post-treatment death/survival. To reduce false positive results, the P value of univariate Cox regression value of each microRNA was evaluated by a permutation test, wherein a patient's survival period, together with censoring status, was randomly permuted for a total of 10,000 iterations.

A mathematical formula was constructed for calculating a risk store for each patient. The formula took into account both the expression levels of one or more of the microRNAs that were identified to be associated with post-treatment death/survival and the regression coefficients derived from the aforementioned univariate Cox regression analyses. See Lossos et al., N. Engl. J. Med. 350:1828-1837; and Cox, 1972. The risk score of a patient correlates with the patient's post-treatment survival period: patients having high risk scores are expected to have shorter survival periods after treatment and patients having low risk scores are expected to live longer after treatment.

All of the patients subjected to this study were assigned to a high-risk group and a low-risk group based on their risk scores. The differences in patient characteristics between the high-risk group and the low-risk group were analyzed using Student's t test for continuous variables or Fisher's exact test for categorical variables. The Kaplan-Meier method was used to estimate the overall survival and relapse-free survival for patients in both groups. The differences as to the overall and replapse-free survival between patients in the two groups were analyzed using the log-rank test. All results thus obtained from the training dataset were validated in patients in the testing dataset and patients in the independent cohort.

Multivariate Cox proportional hazard regression analysis and stepwise variable selection were conducted to evaluate the contribution of independent prognostic factors associated with patient survivals. The microRNA signature risk-score, age, sex, stage and histology were used as covariates. All analyses were performed using SAS version 9.1 software (SAS Institute Inc). Two-tailed tests and P values <0.05 indicates that results are statistically significant.

More details of performing the methods described above can be found in Yu et al., Cancer Cell 13, 48-57 (2008).

Results

(a) Identification and Verification of a MicroRNA Signature for Predicting the Overall Survival and Relapse-Free Survival of NSCLC Patients

Table 1 below shows the clinical characteristics of the 56 NSCLC patients assigned to the training dataset and the 56 NSCLC patients assigned to the testing dataset. There was no significant difference between patients in these two datasets with respect to their clinical characteristics.

The expression levels of microRNAs were determined in all of these patients following the method described above. Results obtained from the training dataset were subjected to univariate Cox regression analysis to identify the microRNAs whose expression levels were associated with post-treatment death/survival. Five microRNAs, i.e., hsa-miR137, hsa-miR372, hsa-miR182*, hsa-miR221, and hsa-let-7a, were found to be associated with overall survival of the patients in the training dataset. Among them, the former three are high-risk microRNAs and the latter two are protective microRNAs.

Based on the expression levels of these five microRNAs, a patient's risk score was calculated following the formula: (0.15×expression level of hsa-miR-137)+(0.31× expression level of hsa-miR-372)+(0.28×expression level of hsa-miR182*)+(−0.13× expression level of hsa-miR-221)+(−0.14×expression level of hsa-let-7a). Patients having a risk score higher than −7.1 were assigned to a high-risk group and patients having a risk score lower than −7.1 were assigned to a low-risk group.

TABLE 1 Clinicopathologic Characteristics of 112 NSCLC Patients Training dataset Testing dataset No. of patients (%) No. of patients (%) Characteristic n = 56 n = 56 P value Age (mean ± SD) 66.5 ± 10.0 65.3 ± 14.1 0.606^(†) Gender Male 45 (80) 43 (77) 0.818^(‡) Female 11 (20) 13 (23) Stage I 21 (38) 26 (46) 0.549^(‡) II 14 (25) 14 (25) III 21 (37) 16 (29) Cell type Adenocarcinoma 25 (45) 30 (53) 0.150^(‡) Squamous cell 25 (45) 25 (45) carcinoma Others  6 (10) 1 (2) ^(†)t test. ^(‡)Fisher's exact test.

The clinical characteristics of the patients in both high-risk and low-risk groups are summarized in Table 2 below.

TABLE 2 Clinical Characteristics of NSCLC Patients in Both The High-Risk and Low- Risk Datasets Characteristic Patients in high-risk group Patients in low-risk group P value Training dataset (n = 56) n = 28 n = 28 Age (mean ± SD) 65.7 ± 10.3 67.3 ± 9.7 0.549^(†) Gender Male 21 (75) 24 (86) 0.503^(‡) Female  7 (25)  4 (14) Stage I  5 (18) 16 (57) 0.008^(‡) II  8 (28)  6 (22) III 15 (54)  6 (21) Cell type Adenocarcinoma 15 (54) 10 (36) 0.353^(‡) Squamous cell carcinoma 10 (36) 15 (54) Others  3 (10)  3 (10) Testing dataset (n = 56) n = 26 n = 30 Age (mean ± SD) 66.5 ± 13.6 64.3 ± 14.7 0.57^(†) Gender Male 22 (85) 21 (70) 0.224^(‡) Female  4 (15)  9 (30) Stage I 11 (42) 15 (50) 0.340^(‡) II  5 (19)  9 (30) III 10 (39)  6 (20) Cell type Adenocarcinoma 17 (65) 13 (43) 0.179^(‡) Squamous cell carcinoma  9 (35) 16 (53) Others 0 (0) 1 (4) Independent cohort (n = 62) n = 40 n = 22 Age (mean ± SD) 62.9 ± 10.3 64.1 ± 9.1 0.634^(†) Gender Male 32 (80) 10 (45) 0.010^(‡) Female  8 (20) 12 (55) Stage I 15 (37) 13 (59) 0.152^(‡) II  6 (15)  4 (18) III 19 (48)  5 (23) Cell type Adenocarcinoma 21 (52)  9 (41) 0.563^(‡) Squamous cell carcinoma 13 (33)  8 (36) Others  6 (15)  5 (23) ^(†)t test. ^(‡)Fisher's exact test.

FIG. 1 shows the risk stores, survival status, and microRNA expression profiles of the NSCLC patients in both the training and testing datasets. Patients having high risk scores express high levels of any of the three high-risk microRNAs and low levels of any of the two protective microRNAs. To the contrary, patients having low risk stores express low levels of any of the high-risk microRNAs and high levels of any of the protective microRNAs.

In the training dataset, the patients in the high-risk group showed shorter post-survival periods than those in the low-risk group. See FIG. 2, Panel A. The median overall survival period of patients in the high-risk group was about 20 month, while that of patients in the low-risk group was longer than 50 months. As to the median relapse-free survival period, it was about 10 month in the high-risk group and longer than 45 months in the low-risk group. See FIG. 2, Panel A. These results indicate that the expression pattern of the five microRNAs mentioned above (i.e., a microRNA signature), based on which a patient is assigned either to the high-risk or the low-risk group, is associated with a cancer patient's post-treatment survival period.

The just-mentioned association between the microRNA signature and survival prospect was verified in the testing dataset. Similar to the results obtained from the training dataset, results obtained from the testing dataset also showed that the patients in the low-risk group lived much longer after treatment than the patients in the high-risk group. See FIG. 2, Panel B. In the high-risk group, the median overall survival period was about 25 month, and the median relapse-free survival period was about 14 month. In the low-risk group, the median overall survival period and relapse-free survival period were longer than 50 months and longer than 40 month, respectively. All these results were statistically significant.

Multivariate Cox regression analysis showed that, among the factors listed in Table 3 below, this microRNA signature was the only factor associated with the overall survival (hazard ratio [HR]=10.31, P=0.002) in NSCLC patients.

TABLE 3 Multivariate Cox Regression* Analysis of The MicroRNA Signature and Survivals in NSCLC Patients Variable Hazard ratio 95% CI P value Overall survival Training dataset (n = 56) microRNA expression signature 10.31  2.33 to 45.56 0.002 Testing dataset (n = 56) microRNA expression signature 3.65  1.29 to 10.37 0.015 Stage 8.12  2.83 to 23.25 <0.001 Age 1.08 1.03 to 1.14 0.002 Independent cohort (n = 62) microRNA expression signature 2.81 1.13 to 7.01 0.026 Stage 2.35 1.13 to 4.89 0.022 Relapse-free survival Training dataset (n = 56) microRNA expression signature 3.29 1.24 to 8.71 0.016 Stage 2.63 1.10 to 6.25 0.029 Testing dataset (n = 56) microRNA expression signature 2.86 1.20 to 6.82 0.018 Stage 2.97 1.32 to 6.69 0.009 Independent cohort (n = 62) microRNA expression signature 2.39 1.12 to 5.10 0.024 Stage 2.76 1.43 to 5.34 0.003 Age 0.93 0.90 to 0.97 <0.001 *Variables were selected through stepwise selection method (b) Validation of the microRNA Signature for Survival Prediction in an Independent Cohort

The microRNA signature mentioned above was validated for its use in predicting post-treatment survival prospect in an independent cohort, including 62 NSCLC patients.

The clinical characteristics of the 62 patients are summarized in Table 2 above. The risk score of each patient was calculated based on his or her expression patterns of the five microRNAs following the method described above. The patients having risk scores higher than −7.1 were assigned to a high-risk group and the patients having risk scores below −7.1 were assigned to a low-risk group. As shown in FIG. 2, Panel C, the patients in the high-risk group had shorter post-treatment survival periods than those in the low-risk group, i.e., 40 months versus longer than 120 months in terms of median overall survival period and 20 months versus 48 months in terms of median relapse-free survival period. See FIG. 2C. Multivariate Cox regression analysis showed that microRNA signature and stage were associated with overall survival and relapse-free survival (see Table 3 supra).

These results confirm that the microRNA signature can be used in predicting a cancer patient's post-treatment survival prospect.

(c) Association between the MicroRNA Signature and Post-Treatment Survival of NSCLC Patients in Different Disease Stages and Histological Subgroups

NSCLC patients in different disease stages and in different histological subgroups were assigned to high-risk and low-risk groups based on their microRNA signature following the method described above. As shown in FIG. 3, the patients in the low-risk groups lived longer after treatment than the patients in the high-risk groups. See Panels A-E. These results indicate that the microRNA signature can also be used to predict the post-treatment survival prospect for NSCLC patients in different disease stages, i.e., stage I, II or III, and in different histological sub-groups, i.e., adenocarcinoma or squamous cell carcinoma sub-groups.

(d) MicroRNA Signatures as Predictors of Patient Survival in NSCLC

Univariate Cox regression analysis showed that the expression level of each of the 5 microRNAs, i.e., hsa-miR137, hsa-miR372, hsa-miR182*, hsa-miR221, or hsa-let-7a, was associated with NSCLC survival. See Table 4 below. The log-rank analysis showed that the microRNA signature composed of all of the five microRNAs is the optimal predictor for patient survival. See also Table 4 below.

In addition, univariate Cox regression analysis showed that a microRNA signature composed of any four of the aforementioned five microRNAs was also associated with patient post-treatment survival. See Table 5 below.

TABLE 4 The P values of log-rank test in Kaplan-Meier survival analysis of the 5- microRNA signature compared to individual microRNA expression in NSCLC patients Training microRNA* dataset Testing dataset Independent cohort Overall survival All five microRNAs <0.001 0.008 0.007 hsa-miR-221 0.021 0.264 0.955 hsa-let-7a 0.906 0.292 0.356 hsa-miR-137 0.026 0.347 0.005 hsa-miR-372 0.358 0.011 <0.001 hsa-miR-182* 0.126 0.005 0.904 Relapse-free survival All five microRNAs 0.002 0.003 0.037 hsa-miR-221 0.008 0.680 0.751 hsa-let-7a 0.258 0.225 0.461 hsa-miR-137 0.086 0.619 0.007 hsa-miR-372 0.615 0.005 0.003 hsa-miR-182* 0.343 0.005 0.961 *two groups were separated based on median

TABLE 5 The P values of Log-Rank Test in Kaplan-Meier Survival Analysis of The 5- microRNA Signature Versus 4-microRNA Signatures in NSCLC Patients Training dataset Testing dataset Independent cohort Overall survival All five microRNAs <0.001 0.008 0.007 Four of the five microRNAs hsa-miR137, hsa-miR372, hsa-miR182*, <0.001 0.007 0.022 and hsa-let-7a hsa-miR137, hsa-miR372, hsa-miR182*, 0.001 0.006 0.057 and hsa-miR221 hsa-miR372, hsa-miR182*, hsa-miR221, 0.020 0.038 0.058 and hsa-let-7a hsa-miR137, hsa-miR182*, hsa-miR221, 0.022 0.141 0.100 and hsa-let-7a hsa-miR137, hsa-miR372, hsa-miR221, or <0.001 0.204 0.003 hsa-let-7a Relapse-free survival All five microRNAs 0.002 0.003 0.037 Four of the five microRNAs hsa-miR137, hsa-miR372, hsa-miR182*, 0.012 0.013 0.078 and hsa-let-7a hsa-miR137, hsa-miR372, hsa-miR182*, 0.033 0.008 0.154 and hsa-miR221 hsa-miR372, hsa-miR182*, hsa-miR221, 0.139 0.006 0.189 and hsa-let-7a hsa-miR137, hsa-miR182*, hsa-miR221, 0.037 0.441 0.116 and hsa-let-7a hsa-miR137, hsa-miR372, hsa-miR221, or <0.001 0.048 0.015 hsa-let-7a (e) Putative Gene Targets of microRNAs

GeneSpring pathway annotated software (Silicon Genetics) was applied to predict the putative pathways that the five microRNAs might be involved and the results thus obtained are summarized in Tables 6 and 7 below.

TABLE 6 Predicted Target Genes of The microRNAs GO Gene GO biological GO molecular cellular microRNA Symbol UniGene Algorithms* Pathways^(†) process function component let-7a ABCB9 Hs.511951 4 ABC transporters - GO: 6857 GO: 5524 GO: 43190 General 02010 GO: 15031 GO: 16887 GO: 5783 GO: 7283 GO: 42626 GO: 16021 GO: 166 GO: 5764 GO: 15198 GO: 5215 let-7a ABCC10 Hs.55879 4 ABC transporters - GO: 6810 GO: 5524 GO: 16021 General 02010 GO: 16887 GO: 42626 GO: 166 let-7a ABCC5 Hs.368563 4 ABC transporters - GO: 6810 GO: 5524 GO: 16021 General 02010 GO: 16887 GO: 5887 GO: 42626 GO: 5624 GO: 15239 GO: 166 GO: 8514 let-7a ATP2A2 Hs.506759 4 Calcium signaling GO: 6816 GO: 5524 GO: 5887 pathway 04020 GO: 6812 GO: 48155 GO: 16020 GO: 7155 GO: 5509 GO: 5624 GO: 8544 GO: 5388 GO: 5792 GO: 8152 GO: 16787 GO: 16529 GO: 15992 GO: 16820 GO: 287 GO: 166 let-7a BZW1 Hs.355983 4 GO: 6446 GO: 3743 let-7a CDC25A Hs.1634 4 Cell cycle 04110; Cell GO: 51301 GO: 16787 GO: 8372 Cycle 69278; Cell Cycle GO: 8283 GO: 4725 GO: 5622 Checkpoints 69620 GO: 7067 GO: 6470 GO: 79 let-7a CHD4 Hs.162233 4 GO: 6333 GO: 5524 GO: 785 GO: 16568 GO: 4003 GO: 5634 GO: 7001) GO: 3677 GO: 6357 GO: 3682 GO: 6350 GO: 16787 GO: 46872 GO: 166 GO: 5515 GO: 8270 let-7a CHD9 Hs.59159 4 GO: 6333 GO: 5524 GO: 785 GO: 3677 GO: 16021 GO: 3682 GO: 5634 GO: 4386 let-7a CHRD Hs.166186 4 TGF-beta signaling GO: 7275 GO: 5554 GO: 8372 pathway 04350 GO: 1501 let-7a DHX57 Hs.468226 4 let-7a DTX2 Hs.187058 4 Notch signaling pathway GO: 7219 GO: 46872 GO: 5634 04330 GO: 16567 GO: 4842 GO: 151 GO: 8270 let-7a E2F5 Hs.445758 4 Cell cycle 04110; TGF- GO: 74 GO: 6355 GO: 5515 GO: 5634 beta signaling pathway GO: 6350 GO: 3700 GO: 5667 04350; Cell Cycle 69278 let-7a EZH2 Hs.444082 4 GO: 6325 GO: 3677 GO: 5634 GO: 6355 GO: 6350 let-7a FASLG Hs.2007 4 Apoptosis 04210; GO: 6915 GO: 5164 GO: 5615 Cytokine-cytokine GO: 7267 GO: 5887 receptor interaction GO: 6955 GO: 16020 04060; MAPK signaling GO: 6917 pathway 04010; Natural GO: 43123 killer cell mediated GO: 7165 cytotoxicity 04650; Type I diabetes mellitus 04940; Apoptosis 109581 let-7a GALE Hs.557524 4 Galactose metabolism GO: 5975 GO: 51287 00052; Nucleotide GO: 6012 GO: 3978 sugars metabolism GO: 9225 GO: 3824 00520; Metabolism of GO: 16853 sugars 71387 let-7a GIPC1 Hs.6454 4 mRNA processing GO: 7186 GO: 5515 GO: 5829 GO: 5102 GO: 16020 GO: 5624 GO: 5625 let-7a GOLT1B Hs.62275 4 GO: 43123 GO: 4871 GO: 16021 GO: 16192 let-7a HOXC11 Hs.127562 4 GO: 7275 GO: 3702 GO: 5634 GO: 7492 GO: 3700 GO: 6355 let-7a IDH2 Hs.513141 4 Krebs-TCA Cycle; Citrate cycle; Glutathione metabolism; Reductive carboxylate cycle let-7a JMJD1A Hs.531819 4 let-7a LOC151579 Hs.529231 4 let-7a LRIG3 Hs.253736 4 let-7a MAP4K3 Hs.468239 4 MAPK signaling GO: 7254 GO: 5524 pathway 04010 GO: 6468 GO: 166 GO: 7243 GO: 4674 GO: 6950 GO: 5083 GO: 16740 let-7a MESDC1 Hs.513071 4 let-7a MLL5 Hs.567540 4 GO: 6355 GO: 5515 GO: 8270 let-7a NDST2 Hs.225129 4 Chondroitin/Heparan GO: 8146 GO: 5795 sulfate biosynthesis GO: 16740 GO: 16021 00532 let-7a NID2 Hs.369840 4 GO: 7155 GO: 5509 GO: 5604 GO: 7160 GO: 5518 GO: 16020 let-7a PBX3 Hs.428027 4 GO: 7387 GO: 5515 GO: 5634 GO: 9790 GO: 3700 GO: 30902 GO: 7388 GO: 6355 GO: 45898 let-7a RANBP2 Hs.199561 4 GO: 46907 GO: 8536 GO: 5643 GO: 6457 GO: 5488 GO: 5634 GO: 6606 GO: 16853 GO: 46872 GO: 3755 GO: 8270 let-7a RFXDC1 Hs.352276 4 GO: 6355 GO: 3677 GO: 214 GO: 6388 GO: 213 GO: 6350 let-7a SEMA4C Hs.516220 4 Axon guidance 04360 GO: 30154 GO: 4872 GO: 16021 GO: 7399 GO: 16020 let-7a SLC20A1 Hs.187946 4 let-7a SLC35D2 Hs.494556 4 GO: 4 GO: 5338 GO: 8372 let-7a SOCS1 Hs.50640 4 Insulin signaling GO: 7259 GO: 5159 GO: 5737 pathway 04910; Jak- GO: 7242 GO: 19901 STAT signaling pathway GO: 46426 GO: 4860 04630; Type II diabetes GO: 1558 mellitus 04930 GO: 6512 let-7a STXBP5 Hs.93534 4 let-7a TMEM2 Hs.494146 4 GO: 16021 let-7a TRAPPC1 Hs.24379 4 let-7a TSCOT Hs.512668 4 let-7a TUSC2 Hs.517981 4 let-7a UHRF2 Hs.493401 4 let-7a USP21 Hs.8015 4 GO: 6512 GO: 4197 GO: 8372 GO: 6511 GO: 8233 GO: 5515 GO: 4221 let-7a USP32 Hs.132868 4 GO: 6512 GO: 5509 GO: 6511 GO: 4197 GO: 4221 let-7a ACTA1 Hs.1288 3 Smooth muscle GO: 7517 GO: 43531 GO: 5884 contraction; Striated GO: 30240 GO: 5524 GO: 5856 muscle contraction GO: 3774 GO: 1725 GO: 17022 GO: 5865 GO: 166 GO: 5515 GO: 5200 let-7a ACVR1B Hs.438918 3 Adherens junction GO: 6468 GO: 5524 GO: 5887 04520; Cytokine- GO: 7178 GO: 287 GO: 16020 cytokine receptor GO: 30145 interaction 04060; GO: 166 MAPK signaling GO: 4674 pathway 04010; TGF- GO: 4872 beta signaling pathway GO: 16740 04350 GO: 5024 let-7a ADAM15 Hs.312098 3 GO: 7155 GO: 17124 GO: 16021 GO: 7160 GO: 46872 GO: 6508 GO: 4222 GO: 5515 GO: 8270 let-7a ADRB2 Hs.2551 3 Calcium signaling GO: 7186 GO: 4941 GO: 5768 pathway 04020; GO: 7188 GO: 5515 GO: 5887 Neuroactive ligand- GO: 187 GO: 4872 GO: 5764 receptor interaction GO: 7190 GO: 1584 GO: 5886 04080 GO: 8333 GO: 7243 GO: 6898 GO: 7171) let-7a ANKFY1 Hs.513875 3 GO: 6897 GO: 46872 GO: 10008 GO: 5515 GO: 16020 GO: 8270 let-7a ANKRD43 Hs.13308 3 let-7a AP1S1 Hs.489365 3 GO: 6886 GO: 5515 GO: 30121 GO: 6898 GO: 8565 GO: 5795 GO: 5802 GO: 5905 let-7a APBB3 Hs.529449 3 GO: 5515 GO: 5737 let-7a ARHGAP20 Hs.6136 3 let-7a ARL5 Hs.470233 3 GO: 6886 GO: 5525 GO: 7264 GO: 166 let-7a ARMC8 Hs.266826 3 let-7a ATXN1 Hs.434961 3 GO: 3723 GO: 5737 GO: 5634 let-7a B3GNT6 Hs.8526 3 Blood group glycolipid GO: 30311 GO: 8532 GO: 5795 biosynthesis- GO: 16757 GO: 30173 neolactoseries 00602; GO: 16021 Keratan sulfate biosynthesis 00533 let-7a BCL2L1 Hs.516966 3 Amyotrophic lateral GO: 6916 GO: 42802 GO: 16021 sclerosis 05030; GO: 8637 GO: 16020 Apoptosis 04210; Jak- GO: 8634 GO: 5741 STAT signaling pathway GO: 42981 GO: 5739 04630; Neurodegenerative Disorders 01510; Apoptosis 109581 let-7a BNC2 Hs.435309 3 GO: 6355 GO: 46872 GO: 5634 GO: 6350 GO: 3676 GO: 8270 let-7a BRD3 Hs.522472 3 GO: 4 GO: 5554 GO: 5634 let-7a BTBD3 Hs.244590 3 GO: 5515 let-7a BTG2 Hs.519162 3 GO: 6281 GO: 3700 GO: 8285 GO: 6355 GO: 6350 let-7a BZW2 Hs.487635 3 let-7a C1orf22 Hs.523811 3 Aminosugars GO: 5975 GO: 5509 GO: 5783 metabolism 00530; GO: 6487 GO: 16798 GO: 16020 Glycosaminoglycan GO: 6508 GO: 4571 degradation 00531; GO: 8233 Nucleotide sugars metabolism 00520 let-7a CALU Hs.7753 3 GO: 4 GO: 5509 GO: 5794 GO: 5783 let-7a CAP1 Hs.370581 3 GO: 7190 GO: 3779 GO: 16020 GO: 7163 GO: 7165 let-7a CASKIN1 Hs.530863 3 GO: 7165 GO: 5515 GO: 5737 let-7a CDC34 Hs.514997 3 Ubiquitin mediated proteolysis let-7a CDYL Hs.269092 3 GO: 6333 GO: 3824 GO: 785 GO: 8152 GO: 3682 GO: 5634 GO: 7283 GO: 8233 let-7a COIL Hs.532795 3 GO: 5634 let-7a COL15A1 Hs.409034 3 GO: 1525 GO: 5515 GO: 5582 GO: 7155 GO: 5198 GO: 5737 GO: 30154 GO: 5578) GO: 6817 let-7a COL1A1 Hs.172928 3 Cell Communication GO: 8544 GO: 5201 GO: 5581 01430; ECM-receptor GO: 6817 GO: 8147 GO: 5584 interaction 04512; Focal GO: 7605 GO: 5737 adhesion 04510; GO: 1501 Hemostasis 109582 let-7a COL1A2 Hs.489142 3 Cell Communication GO: 4 GO: 6817 GO: 5201 GO: 5581 01430; ECM-receptor GO: 7605 GO: 8147 GO: 5584 interaction 04512; Focal GO: 1501 GO: 5737 adhesion 04510; GO: 7169 Hemostasis 109582 let-7a COL24A1 Hs.47312 3 let-7a COL3A1 Hs.443625 3 Inflammatory Response Pathway let-7a COL4A1 Hs.17441 3 GO: 6817 GO: 5201 GO: 5581 GO: 5587 GO: 5737 let-7a COL4A2 Hs.508716 3 let-7a COL4A5 Hs.369089 3 let-7a CPA4 Hs.93764 3 GO: 16573 GO: 4182 GO: 8372 GO: 6508 GO: 4180 GO: 46872 GO: 8237 GO: 8270 let-7a CPD Hs.446079 3 GO: 6508 GO: 4182 GO: 16021 GO: 4187 GO: 5624 GO: 4180 GO: 46872 GO: 8472 GO: 8237 GO: 8270 let-7a CPEB2 Hs.374216 3 let-7a CPEB3 Hs.131683 3 GO: 3676 GO: 166 let-7a CPEB4 Hs.127126 3 let-7a CPM Hs.434948 3 let-7a CPSF4 Hs.489287 3 mRNA processing GO: 6397 GO: 3723 GO: 5634 GO: 46872 GO: 8270 let-7a CTNS Hs.187667 3 GO: 15811 GO: 15184 GO: 16021 GO: 6520 GO: 5765 GO: 6810 let-7a CYP46A1 Hs.25121 3 GO: 6707 GO: 20037 GO: 5783 GO: 6118 GO: 5506 GO: 16021 GO: 6629 GO: 46872 GO: 5792 GO: 7399 GO: 8395 GO: 8202 let-7a DDEF1 Hs.106015 3 GO: 43087 GO: 5096 GO: 16020 GO: 46872 GO: 5515 GO: 8270 let-7a DDX19 Hs.221761 3 let-7a DIMT1L Hs.533222 3 let-7a DLC1 Hs.134296 3 GO: 7010 GO: 5100 GO: 5737 GO: 30308 GO: 5515 GO: 5576 GO: 30155 GO: 7165 let-7a DMD Hs.495912 3 Striated muscle GO: 4 GO: 7016 GO: 3779 GO: 8372 contraction GO: 6936 GO: 5509 GO: 5856 GO: 7517 GO: 5554 GO: 16010 GO: 5515 GO: 5200 GO: 8307 GO: 5198 GO: 8270 let-7a DMP1 Hs.128556 3 GO: 7155 GO: 5509 GO: 5578) GO: 30198 GO: 5178 GO: 1503 let-7a DMTF1 Hs.558441 3 let-7a DOT1L Hs.465554 3 Lysine degradation GO: 16568 GO: 18024 GO: 5634 00310 GO: 8168 GO: 16740 let-7a DPF2 Hs.13495 3 GO: 6915 GO: 46872 GO: 5634 GO: 8624 GO: 3676 GO: 6355 GO: 5515 GO: 6350 GO: 8270 let-7a DPP3 Hs.502914 3 GO: 6508 GO: 4177 GO: 5737 GO: 17039 GO: 46872 GO: 8237 GO: 8270 let-7a DST Hs.485616 3 GO: 30036 GO: 3779 GO: 5604 GO: 7155 GO: 51015 GO: 5737 GO: 7050 GO: 5509 GO: 16023 GO: 7010 GO: 5178 GO: 5856 GO: 7229 GO: 8022 GO: 5615 GO: 45104 GO: 5515 GO: 30056 GO: 5200 GO: 5911 let-7a DUSP1 Hs.171695 3 ; Calcium signaling pathway; Type I diabetes mellitus;; Calcium signaling pathway let-7a DUSP16 Hs.536535 3 MAPK signaling GO: 45204 GO: 17017 GO: 5737 pathway 04010 GO: 45209 GO: 16787 GO: 5634 GO: 188 GO: 6470 let-7a DUSP9 Hs.144879 3 MAPK signaling GO: 7254 GO: 17017 GO: 5737 pathway 04010 GO: 188 GO: 16787 GO: 5634 GO: 6470 let-7a DYRK1A Hs.368240 3 Benzoate degradation via GO: 7399 GO: 5524 GO: 5634 CoA ligation 00632; GO: 18108 GO: 4715 Inositol phosphate GO: 166 metabolism 00562; GO: 4674 Nicotinate and GO: 16740 nicotinamide metabolism 00760; Phosphatidylinositol signaling system 04070 let-7a EGR3 Hs.534313 3 GO: 7623 GO: 46872 GO: 5634 GO: 7517 GO: 3700 GO: 6355 GO: 8270 GO: 6350 let-7a EIF2C1 Hs.22867 3 GO: 6412 GO: 5515 GO: 5850 GO: 6446 GO: 3743 let-7a EIF2C3 Hs.567761 3 GO: 6412 GO: 3743 let-7a EIF2C4 Hs.471492 3 GO: 6412 GO: 3743 let-7a EPHA3 Hs.123642 3 Axon guidance 04360 GO: 6468 GO: 5524 GO: 5887 GO: 7165 GO: 5003 GO: 16020 GO: 7169 GO: 166 GO: 4674 GO: 4713 GO: 4872 GO: 16740 let-7a EPHA4 Hs.371218 3 Calcium signaling pathway let-7a ERCC6 Hs.133444 3 DNA Repair 73894 GO: 6281 GO: 5524 GO: 5634 GO: 6355 GO: 3677 GO: 7605 GO: 3678 GO: 6350 GO: 3702 GO: 6366 GO: 4386 GO: 16787 GO: 166 GO: 5515 let-7a FARP1 Hs.567409 3 GO: 7155 GO: 8092 GO: 5737 GO: 5085 GO: 5856 GO: 16020 let-7a FBXL19 Hs.152149 3 GO: 6508 GO: 3677 GO: 5737 GO: 6355 GO: 46872 GO: 6512 GO: 5515 GO: 4842 GO: 8270 let-7a FGF11 Hs.528468 3 let-7a FLJ21986 Hs.189652 3 let-7a FNDC3A Hs.508010 3 ECM-receptor interaction 04512 let-7a FRAS1 Hs.369448 3 let-7a GALNT1 Hs.514806 3 O-Glycan biosynthesis GO: 6493 GO: 5509 GO: 5795 00512 GO: 30145 GO: 16021 GO: 4653 GO: 5529 GO: 16757 let-7a GATM Hs.75335 3 Urea cycle and metabolism of amino groups; Glycine, serine and threonine metabolism; Arginine and proline metabolism let-7a GGA3 Hs.87726 3 GO: 6886 GO: 30306 GO: 5795 GO: 6461 GO: 5515 GO: 5802 GO: 8565 GO: 30130 GO: 16020 let-7a GNAL Hs.136295 3 Calcium signaling GO: 7186 GO: 5525 pathway 04020 GO: 7165 GO: 3924 GO: 166 GO: 4871 let-7a GNG5 Hs.554749 3 Energy Metabolism GO: 7186 GO: 4871 GO: 5834 163685 GO: 7165 let-7a GNPTAB Hs.46850 3 let-7a GRIK2 Hs.98262 3 Neuroactive ligand- GO: 7215 GO: 5234 GO: 5887 receptor interaction GO: 6811 GO: 5216 GO: 16020 04080 GO: 6813 GO: 4970 GO: 45211 GO: 7268 GO: 15277 GO: 6810 GO: 5267 GO: 4872 GO: 5215 let-7a HAND1 Hs.152531 3 GO: 7275 GO: 3700 GO: 5634 GO: 7507 GO: 6355 GO: 6366 let-7a HAS2 Hs.159226 3 GO: 50501 GO: 5887 GO: 16757 let-7a HDHD1A Hs.185910 3 GO: 4 GO: 8152 GO: 3824 GO: 8372 GO: 5554 let-7a HECTD2 Hs.535293 3 GO: 15671 GO: 20037 GO: 5622 GO: 6512 GO: 5344 GO: 4842 let-7a HIC2 Hs.517434 3 GO: 45892 GO: 3677 GO: 5634 GO: 6350 GO: 46872 GO: 8022 GO: 8270 let-7a HOMER2 Hs.459142 3 GO: 7216 let-7a HOXA9 Hs.127428 3 GO: 4 GO: 7275 GO: 5554 GO: 5634 GO: 6355 GO: 3700 GO: 16563 let-7a HOXB4 Hs.532669 3 GO: 7275 GO: 3700 GO: 5634 GO: 6355 let-7a HOXD1 Hs.83465 3 GO: 7275 GO: 3700 GO: 5634 GO: 6355 let-7a HTR4 Hs.483773 3 Calcium signaling GO: 7187 GO: 4935 GO: 5887 pathway 04020; GO: 7165 GO: 4872 Neuroactive ligand- GO: 1584 receptor interaction GO: 4993 04080 let-7a IL13 Hs.845 3 Cytokine-cytokine GO: 19735) GO: 8009 GO: 5615 receptor interaction GO: 6928 GO: 5144 GO: 5625 04060; Jak-STAT GO: 8283 GO: 4871 signaling pathway 04630 GO: 7267 GO: 6954 GO: 7165 let-7a INPP5A Hs.523360 3 Inositol phosphate GO: 7154 GO: 16787 GO: 16020 metabolism 00562; GO: 4437 Phosphatidylinositol GO: 4445 signaling system 04070 let-7a IRS2 Hs.442344 3 Adipocytokine signaling GO: 6006 GO: 5158 pathway 04920; Insulin GO: 8284 GO: 4871 signaling pathway GO: 7165 04910; Type II diabetes mellitus 04930; Insulin receptor mediated signalling 74752 let-7a ITGB3 Hs.218040 3 ECM-receptor GO: 7596 GO: 42802 GO: 8305 interaction 04512; Focal GO: 7155 GO: 4872 adhesion 04510; GO: 7160 Hematopoietic cell GO: 7275 lineage 04640; GO: 7229 Regulation of actin cytoskeleton 04810; Hemostasis 109582 let-7a KCNC2 Hs.27214 3 let-7a KIF1B Hs.97858 3 GO: 8089 GO: 5524 GO: 30659 GO: 9790 GO: 16887 GO: 5874 GO: 7018 GO: 19894 GO: 5875 GO: 7270 GO: 8017 GO: 5739 GO: 7274 GO: 3777 GO: 166 GO: 5515 let-7a KIF2 Hs.558351 3 GO: 7018 GO: 5524 GO: 5856 GO: 3777 GO: 5874 GO: 166 GO: 5875 let-7a KLF9 Hs.150557 3 Circadian Exercise GO: 6357 GO: 46872 GO: 5634 GO: 6350 GO: 3700 GO: 8270 let-7a KPNA4 Hs.288193 3 GO: 6607 GO: 5488 GO: 5634 GO: 6886 GO: 8565 let-7a LOC283859 Hs.298434 3 Wnt signaling pathway 04310 let-7a LOC643176 Hs.403917 3 let-7a LOXL3 Hs.469045 3 let-7a LOXL4 Hs.306814 3 Arginine and proline GO: 5507 GO: 16020 metabolism 00330 GO: 46872 GO: 16491 GO: 4720 GO: 5044 let-7a LRIG1 Hs.518055 3 let-7a LRIG2 Hs.448972 3 let-7a MAP3K7IP2 Hs.269775 3 MAPK signaling pathway 04010; Toll-like receptor signaling pathway 04620 let-7a MED6 Hs.497353 3 MED6 GO: 45944 GO: 3702 GO: 119 GO: 4872 GO: 5634 GO: 3713 let-7a MEF2D Hs.314327 3 GO: 7517 GO: 3713 GO: 5634 GO: 6355 GO: 3700 GO: 6350 GO: 6366 let-7a MEIS2 Hs.510989 3 GO: 122 GO: 3704 GO: 5634 GO: 6355 GO: 3714 GO: 3700 let-7a MGAT4A Hs.177576 3 N-Glycan biosynthesis let-7a MTPN Hs.43297 3 let-7a MYCN Hs.25960 3 GO: 6357 GO: 5515 GO: 785 GO: 3700 GO: 5634 let-7a NAB1 Hs.107474 3 GO: 16481 GO: 3676 GO: 5634 GO: 6355 GO: 16564 GO: 6350 let-7a NCOA3 Hs.382168 3 GO: 30521 GO: 8415 GO: 5634 GO: 45893 GO: 50681 GO: 7165 GO: 4402 GO: 5515 GO: 4871 GO: 46966 GO: 3713 GO: 30528 GO: 16740 let-7a NLK Hs.208759 3 Adherens junction GO: 30178 GO: 5524 GO: 5634 04520; MAPK signaling GO: 6468 GO: 4707 pathway 04010; Wnt GO: 7243 GO: 287 GO: 166 signaling pathway 04310 GO: 6355 GO: 5515 GO: 4674 GO: 4713 GO: 16740 let-7a NME4 Hs.9235 3 let-7a NPHP3 Hs.511991 3 let-7a NUMBL Hs.326953 3 Notch signaling pathway GO: 7399 04330 let-7a NUP98 Hs.524750 3 GO: 6260 GO: 5515 GO: 5643 GO: 6999 GO: 17056 GO: 5654 GO: 6913 GO: 59 GO: 5215 GO: 15031 let-7a OPRM1 Hs.2353 3 Neuroactive ligand- GO: 7186 GO: 4988 GO: 5794 receptor interaction GO: 7187 GO: 4872 GO: 5783 04080 GO: 7610 GO: 1584 GO: 16021 GO: 8285 GO: 5887 GO: 7600 GO: 5886 GO: 7165 let-7a P4HA2 Hs.519568 3 Arginine and proline GO: 19538 GO: 31418 GO: 5783 metabolism 00330 GO: 5489 GO: 5506 GO: 46872 GO: 16491 GO: 16706 GO: 16702 GO: 4656 GO: 5515 let-7a PAK1 Hs.435714 3 Axon guidance 04360; GO: 7254 GO: 5524 Focal adhesion 04510; GO: 6915 GO: 166 MAPK signaling GO: 6468 GO: 5515 pathway 04010; Natural GO: 4674 killer cell mediated GO: 4713 cytotoxicity 04650; GO: 16740 Regulation of actin cytoskeleton 04810; T cell receptor signaling pathway 04660 let-7a PANX2 Hs.440092 3 GO: 5921 GO: 16021 let-7a PAPPA Hs.494928 3 GO: 30154 GO: 46872 GO: 5615 GO: 7565 GO: 8237 GO: 16020 GO: 6508 GO: 8270 let-7a PAX3 Hs.42146 3 GO: 6915 GO: 3700 GO: 5634 GO: 7275 GO: 7399 GO: 9887 GO: 6355 GO: 7605 GO: 6366 let-7a PBX2 Hs.509545 3 GO: 7387 GO: 5515 GO: 5634 GO: 7388 GO: 3700 GO: 6355 let-7a PDGFB Hs.1976 3 Cytokine-cytokine GO: 8283 GO: 74 GO: 8083 GO: 5576 receptor interaction GO: 9611 GO: 5161 GO: 16020 04060; Focal adhesion 04510; Gap junction 04540; MAPK signaling pathway 04010; Regulation of actin cytoskeleton 04810; Hemostasis 109582 let-7a PHF8 Hs.133352 3 GO: 6355 GO: 46872 GO: 5515 GO: 8270 let-7a PLAGL2 Hs.154104 3 GO: 6355 GO: 46872 GO: 5634 GO: 6350 GO: 3700 GO: 8270 let-7a PLCB4 Hs.472101 3 Calcium signaling GO: 7242 GO: 5509 pathway 04020; Gap GO: 16042 GO: 16787 junction 04540; Inositol GO: 6629 GO: 4435 phosphate metabolism GO: 4871 00562; Phosphatidylinositol signaling system 04070; Wnt signaling pathway 04310 let-7a PLD3 Hs.257008 3 GO: 8152 GO: 3824 let-7a PLEKHG6 Hs.163953 3 GO: 5085 let-7a PLEKHO1 Hs.438824 3 let-7a PLGLB2 Hs.528525 3 let-7a POGZ Hs.489873 3 GO: 7275 GO: 3677 GO: 5634 GO: 46872 GO: 3676 GO: 8270 let-7a POLH Hs.439153 3 let-7a PPARGC1A Hs.527078 3 Adipocytokine signaling GO: 8380 GO: 3677 GO: 5665 pathway 04920; Insulin GO: 30521 GO: 3723 GO: 5634 signaling pathway 04910 GO: 50873 GO: 16455 GO: 1678 GO: 50681 GO: 45333 GO: 30374 GO: 7586 GO: 166 GO: 19395 GO: 8134 GO: 6094 GO: 6397 GO: 7005 GO: 46321 GO: 45722 GO: 35066 GO: 45893 GO: 6461 GO: 50821 GO: 42594 GO: 1659 GO: 6350 GO: 6367 let-7a PPP3CA Hs.435512 3 Amyotrophic lateral GO: 6470 GO: 5509 GO: 5955 sclerosis 05030; GO: 5516 GO: 5634 Apoptosis 04210; Axon GO: 16787 guidance 04360; B cell GO: 5506 receptor signaling GO: 4722 pathway 04662; Calcium GO: 8270 signaling pathway 04020; MAPK signaling pathway 04010; Natural killer cell mediated cytotoxicity 04650; T cell receptor signaling pathway 04660; Wnt signaling pathway 04310 let-7a PRDM2 Hs.371823 3 GO: 6355 GO: 46872 GO: 5634 GO: 3676 GO: 3700 GO: 8270 let-7a PRRX1 Hs.283416 3 let-7a PTPRU Hs.19718 3 GO: 7155 GO: 16787 GO: 5887 GO: 6470 GO: 4725 GO: 16020 GO: 7185 GO: 4872 GO: 5001 let-7a PYGO2 Hs.433795 3 let-7a QARS Hs.79322 3 Aminoacyl-tRNA GO: 6425 GO: 5524 GO: 5737 synthetases 00970; GO: 6424 GO: 4818 GO: 5625 Glutamate metabolism GO: 6412 GO: 4819 00251 GO: 16874 GO: 166 GO: 5515 let-7a RAI16 Hs.491223 3 let-7a RAPGEF6 Hs.483329 3 let-7a RASL10B Hs.437035 3 let-7a RB1 Hs.408528 3 Cell cycle 04110; Cell GO: 30521 GO: 50681 GO: 785 Cycle 69278 GO: 75 GO: 5554 GO: 5634 GO: 45786 GO: 5515 GO: 6469 GO: 3713 GO: 122 GO: 3700 GO: 45893 GO: 6355 GO: 6350 let-7a RBM9 Hs.282998 3 Ribosomal Proteins let-7a RDH10 Hs.244940 3 let-7a RDX Hs.263671 3 Regulation of actin GO: 51016 GO: 3779 GO: 15629 cytoskeleton 04810 GO: 7016 GO: 5488 GO: 5737 GO: 5198 GO: 5886 let-7a RGAG1 Hs.201071 3 let-7a RNF20 Hs.168095 3 GO: 16567 GO: 46872 GO: 151 GO: 4842 GO: 8270 let-7a RNF38 Hs.333503 3 GO: 16567 GO: 46872 GO: 151 GO: 4842 GO: 8270 let-7a RNF44 Hs.434888 3 GO: 16567 GO: 46872 GO: 151 GO: 4842 GO: 8270 let-7a RNF5 Hs.534342 3 GO: 16567 GO: 46872 GO: 151 GO: 5515 GO: 4842 GO: 8270 let-7a RUFY3 Hs.7972 3 let-7a SCN5A Hs.556087 3 GO: 6812 GO: 5261 GO: 16021 GO: 6936 GO: 31402 GO: 16020 GO: 8016 GO: 5248 GO: 5624 GO: 6814 GO: 1518 let-7a SCUBE3 Hs.12923 3 let-7a SEC24C Hs.81964 3 GO: 6888 GO: 3779 GO: 30127 GO: 6886 GO: 5554 GO: 5795 GO: 5515 GO: 5783 let-7a SEMA3F Hs.32981 3 Axon guidance 04360 GO: 7275 GO: 5615 let-7a SEMA4G Hs.567556 3 Axon guidance 04360 GO: 30154 GO: 4872 GO: 16021 GO: 7399 GO: 16020 let-7a SENP2 Hs.401388 3 Wnt signaling pathway GO: 6508 GO: 16929 GO: 5643 04310 GO: 30111 GO: 8234 GO: 5634 GO: 6512 GO: 5515 let-7a SENP5 Hs.533124 3 let-7a SFRS12 Hs.519347 3 mRNA processing let-7a SLC25A18 Hs.282982 3 GO: 6810 GO: 5488 GO: 16021 GO: 15293 GO: 5743 GO: 5739 let-7a SLC25A18 Hs.570482 3 GO: 6810 GO: 5488 GO: 16021 GO: 15293 GO: 5743 GO: 5739 let-7a SLC25A4 Hs.246506 3 Calcium signaling GO: 6091 GO: 2 GO: 15207 GO: 16021 pathway 04020; GO: 6839 GO: 5488 GO: 5887 Nucleotide metabolism GO: 6810 GO: 5215 GO: 16020 15869 GO: 5743 GO: 5739 let-7a SLC4A4 Hs.5462 3 GO: 6820 GO: 5452 GO: 16021 GO: 6810 GO: 8510 GO: 5887 GO: 16020 let-7a SLC6A1 Hs.443874 3 let-7a SLC6A15 Hs.44424 3 GO: 6836 GO: 5328 GO: 5887 GO: 15293 GO: 16020 let-7a SLCO5A1 Hs.443609 3 GO: 6810 GO: 5215 GO: 16021 GO: 16020 let-7a SMARCAD1 Hs.410406 3 let-7a SMARCC1 Hs.476179 3 GO: 6333 GO: 3677 GO: 16514 GO: 6338 GO: 3682 GO: 785 GO: 45893 GO: 5515 GO: 5654 GO: 45449 GO: 3713 GO: 5634 GO: 6357 let-7a SPATA2 Hs.48513 3 GO: 30154 GO: 5554 GO: 5737 GO: 7283 let-7a STARD13 Hs.507704 3 let-7a STRBP Hs.287659 3 let-7a SYT1 Hs.310545 3 let-7a TAF5 Hs.96103 3 RNA transcription let-7a TARBP2 Hs.326 3 GO: 6469 GO: 3725 GO: 5622 GO: 45946 GO: 46982 GO: 5634 GO: 45070 GO: 6357 GO: 46782 let-7a TBX5 Hs.381715 3 GO: 7507 GO: 3702 GO: 5634 GO: 9653 GO: 5515 GO: 45893 GO: 3700 GO: 6355 GO: 6350 let-7a TGFBR1 Hs.494622 3 Adherens junction GO: 6468 GO: 5524 GO: 16021 04520; Cytokine- GO: 7165 GO: 287 GO: 5887 cytokine receptor GO: 7181 GO: 30145 GO: 16020 interaction 04060; GO: 7178 GO: 166 MAPK signaling GO: 4713 pathway 04010; TGF- GO: 4872 beta signaling pathway GO: 16740 04350 GO: 5024 GO: 5025 let-7a TIMM17B Hs.30570 3 GO: 6626 GO: 15450 GO: 16021 GO: 5744 GO: 5739 let-7a Transcribed Hs.408973 3 locus let-7a Transcribed Hs.560163 3 locus let-7a TRIB2 Hs.467751 3 GO: 6468 GO: 5524 GO: 5737 GO: 43405 GO: 166 GO: 4674 GO: 4713 GO: 16740 let-7a TRIM41 Hs.441488 3 let-7a TSC22D2 Hs.52526 3 GO: 6355 GO: 3700 let-7a TTLL4 Hs.471405 3 GO: 6464 GO: 16874 GO: 4835 let-7a ULK2 Hs.168762 3 GO: 6468 GO: 5524 GO: 166 GO: 4674 GO: 4713 GO: 16740 let-7a USP25 Hs.473370 3 GO: 6508 GO: 4197 GO: 6512 GO: 4221 GO: 6511 let-7a VAV3 Hs.267659 3 B cell receptor signaling GO: 7242 GO: 5096 pathway 04662; Focal GO: 7264 GO: 5070 adhesion 04510; Natural GO: 19992 killer cell mediated GO: 5085 cytotoxicity 04650; GO: 46872 Regulation of actin GO: 8270 cytoskeleton 04810 let-7a VSNL1 Hs.444212 3 GO: 5509 let-7a WDFY3 Hs.480116 3 let-7a WNT1 Hs.248164 3 Hedgehog signaling GO: 30154 GO: 5102 GO: 5576 pathway 04340; Wnt GO: 1708 GO: 5625 signaling pathway 04310 GO: 16477 GO: 7417 GO: 7163 GO: 7223 GO: 9653 GO: 7283 let-7a XKR8 Hs.55024 3 GO: 16021 let-7a ZC3H3 Hs.521915 3 GO: 46872 GO: 3676 GO: 8270 let-7a ZCCHC5 Hs.134873 3 GO: 46872 GO: 3676 GO: 8270 let-7a ZFYVE26 Hs.98041 3 GO: 3676 GO: 5634 GO: 8270 let-7a ZNF318 Hs.509718 3 GO: 3824 GO: 5634 GO: 3676 GO: 3735 GO: 8270 let-7a ZNF644 Hs.173001 3 GO: 6355 GO: 3677 GO: 5634 GO: 6350 GO: 46872 GO: 8270 let-7a ZZZ3 Hs.480506 3 GO: 45449 GO: 3677 GO: 5634 GO: 8270 miR-182* DOCK9 Hs.314413 4 miR-182* AARS Hs.315137 3 Alanine and aspartate GO: 6419 GO: 5524 GO: 5737 metabolism 00252; GO: 6412 GO: 4813 GO: 5625 Aminoacyl-tRNA GO: 8033 GO: 16874 synthetases 00970 GO: 3676 GO: 166 GO: 49 miR-182* ABCG1 Hs.124649 3 ABC transporters - GO: 42632 GO: 5524 GO: 5795 General 02010 GO: 8203 GO: 16887 GO: 5783 GO: 9720 GO: 42626 GO: 5887 GO: 6869 GO: 15196 GO: 16020 GO: 10033 GO: 166 GO: 5624 GO: 15646 GO: 46983 GO: 15216 miR-182* ALDH18A1 Hs.500645 3 Urea cycle and GO: 8652 GO: 3942 GO: 5739 metabolism of amino GO: 8152 GO: 4349 GO: 19866 groups 00220 GO: 6561 GO: 4350 GO: 16301 GO: 16491 GO: 16740 miR-182* BACH2 Hs.269764 3 GO: 6355 GO: 3677 GO: 5634 GO: 6350 GO: 5515 miR-182* CBX3 Hs.381189 3 Circadian Exercise GO: 6333 GO: 3682 GO: 785 GO: 16568 GO: 5515 GO: 5634 GO: 6355 GO: 6350 miR-182* CD36 Hs.120949 3 Adipocytokine signaling GO: 7596 GO: 5515 GO: 5887 pathway 04920; ECM- GO: 7155 GO: 4872 GO: 16020 receptor interaction GO: 6631 GO: 5624 04512; Hematopoietic GO: 6629 cell lineage 04640; GO: 6810 Hemostasis 109582 miR-182* CRLF1 Hs.114948 3 GO: 19735 + F280 GO: 19955 GO: 5615 GO: 4872 miR-182* CXXC5 Hs.189119 3 GO: 3677 GO: 8270 miR-182* FAT Hs.481371 3 GO: 7155 GO: 5509 GO: 5887 GO: 7267 GO: 5515 GO: 16020 GO: 7156 GO: 9653 miR-182* FBXW11 Hs.484138 3 Hedgehog signaling GO: 16055 GO: 4842 GO: 151 pathway 04340; GO: 16567 Ubiquitin mediated proteolysis 04120; Wnt signaling pathway 04310 miR-182* FYCO1 Hs.200227 3 miR-182* KCMF1 Hs.345694 3 miR-182* GALNT1 Hs.514806 3 O-Glycan biosynthesis GO: 6493 GO: 5509 GO: 5795 00512 GO: 30145 GO: 16021 GO: 4653 GO: 5529 GO: 16757 miR-182* HDAC7A Hs.200063 3 Cell cycle 04110 GO: 30183 GO: 4407 GO: 5737 GO: 16568 GO: 16787 GO: 118 GO: 6954 GO: 16566 GO: 5634 GO: 45843 GO: 8134 GO: 7399 GO: 74 GO: 6355 GO: 6350 miR-182* HDHD2 Hs.465041 3 miR-182* HOXB4 Hs.532669 3 GO: 7275 GO: 3700 GO: 5634 GO: 6355 miR-182* HRMT1L4 Hs.504530 3 Aminophosphonate GO: 8757 GO: 5634 metabolism 00440; GO: 16740 Androgen and estrogen metabolism 00150; Histidine metabolism 00340; Nitrobenzene degradation 00626; Selenoamino acid metabolism 00450; Tryptophan metabolism 00380; Tyrosine metabolism 00350 miR-182* ITGA10 Hs.158237 3 ECM-receptor GO: 7155 GO: 5509 GO: 16021 interaction 04512; Focal GO: 7160 GO: 5518 GO: 8305 adhesion 04510; GO: 7229 GO: 287 Regulation of actin GO: 4872 cytoskeleton 04810 miR-182* LGI1 Hs.533670 3 GO: 8283 GO: 7399 miR-182* MAPK9 Hs.484371 3 Adipocytokine signaling GO: 7254 GO: 5524 pathway 04920; Focal GO: 6468 GO: 4705 adhesion 04510; Insulin GO: 6950 GO: 4707 signaling pathway GO: 166 04910; MAPK signaling GO: 5515 pathway 04010; Toll-like GO: 4674 receptor signaling GO: 4713 pathway 04620; Type II GO: 16740 diabetes mellitus 04930; Wnt signaling pathway 04310 miR-182* PLA2G6 Hs.170479 3 Glycerophospholipid GO: 16042 GO: 16787 GO: 5737 metabolism 00564; GO: 6644 GO: 4623 GO: 16020 MAPK signaling pathway 04010; Prostaglandin and leukotriene metabolism 00590 miR-182* PLAGL2 Hs.154104 3 GO: 6355 GO: 46872 GO: 5634 GO: 6350 GO: 3700 GO: 8270 miR-182* PLCL2 Hs.202010 3 miR-182* RAB5A Hs.475663 3 GO: 6897 GO: 5525 GO: 5769 GO: 6886 GO: 3924 GO: 7264 GO: 166 GO: 5515 miR-182* RAB6A Hs.503222 3 GO: 6888 GO: 5525 GO: 5795 GO: 15031 GO: 3924 GO: 7264 GO: 166 GO: 5515 miR-182* RBM12 Hs.246413 3 miR-182* RPS6KA1 Hs.149957 3 Ribosomal Proteins;; GO: 6468 GO: 5524 Calcium signaling GO: 7165 GO: 166 pathway; GO: 4672 Phosphatidylinositol GO: 4674 signaling system GO: 4713 GO: 3735 GO: 16740 miR-182* SBF1 Hs.449098 3 GO: 46839 GO: 4437 GO: 16021 GO: 6470 GO: 8138 GO: 5634 miR-182* SLC18A1 Hs.158322 3 GO: 15893 GO: 15238 GO: 16021 GO: 15844 GO: 8504 GO: 5624 GO: 15293 miR-182* SMAD7 Hs.465087 3 TGF-beta signaling GO: 6355 GO: 5515 GO: 5634 pathway 04350 GO: 6950 GO: 5076 GO: 6350 GO: 30617 GO: 7179 miR-182* TACR3 Hs.942 3 Calcium signaling GO: 7165 GO: 4872 GO: 5887 pathway 04020; GO: 7217 GO: 1584 GO: 5886 Neuroactive ligand- GO: 4995 receptor interaction 04080 miR-182* TCERG1 Hs.443465 3 GO: 6355 GO: 3702 GO: 5634 GO: 6350 GO: 5515 GO: 6366 GO: 3713 miR-182* TFIP11 Hs.20225 3 GO: 30154 GO: 3676 GO: 5634 GO: 30198 GO: 5515 GO: 1503 GO: 45045 miR-182* TP53INP2 Hs.516994 3 miR-182* UBE2B Hs.385986 3 Ubiquitin mediated GO: 6281 GO: 16874 GO: 16020 proteolysis; GO: 6512 GO: 8642 GO: 5634 GO: 4842 miR-182* VAT1 Hs.514199 3 GO: 16049 GO: 3677 GO: 16021 GO: 16491 GO: 5634 GO: 8270 GO: 8021 miR-182* ZFP36L2 Hs.503093 3 GO: 8283 GO: 46872 GO: 5634 GO: 3676 GO: 3700 GO: 8270 miR-182* ZIC3 Hs.111227 3 GO: 7368 GO: 3677 GO: 5634 GO: 6355 GO: 46872 GO: 6350 GO: 8270 miR-372 ATXN1 Hs.434961 4 GO: 3723 GO: 5737 GO: 5634 miR-372 POLH Hs.439153 4 miR-372 BCL11B Hs.510396 4 GO: 6355 GO: 46872 GO: 5634 GO: 6350 GO: 3676 GO: 8270 miR-372 DPYSL5 Hs.299315 4 Axon guidance 04360 GO: 7411 GO: 16787 GO: 7399 GO: 7165 miR-372 INHBB Hs.1735 4 Cytokine-cytokine GO: 30154 GO: 5125 GO: 5576 receptor interaction GO: 6952 GO: 8083 04060; TGF-beta GO: 40007 GO: 5179 signaling pathway 04350 GO: 46882 GO: 46789 GO: 48178 GO: 42803 GO: 1541 miR-372 MAP3K11 Hs.502872 4 ; Calcium signaling GO: 80 GO: 7257 GO: 5524 GO: 5813 pathway GO: 8283 GO: 4706 GO: 5874 GO: 7017 GO: 166 GO: 46777 GO: 5515 GO: 51259 GO: 42803 GO: 4674 GO: 4713 miR-372 MYCN Hs.25960 4 GO: 6357 GO: 5515 GO: 785 GO: 3700 GO: 5634 miR-372 NEUROD6 Hs.45152 4 GO: 6355 GO: 3677 GO: 5634 GO: 30528 miR-372 NFIB Hs.370359 4 GO: 6260 GO: 3700 GO: 5634 GO: 6355 GO: 6350 miR-372 PARP8 Hs.369581 4 miR-372 CDNA Hs.406990 4 FLJ38785 fis miR-372 RBBP7 Hs.495755 4 GO: 8283 GO: 5515 GO: 5634 GO: 7275 miR-372 SS18L1 Hs.154429 4 GO: 5515 miR-372 TLE4 Hs.444213 4 GO: 4 GO: 7222 GO: 5554 GO: 5634 GO: 6355 miR-372 ADAM9 Hs.2442 3 GO: 7243 GO: 17124 GO: 5887 GO: 6508 GO: 5178 GO: 46872 GO: 4222 GO: 5515 GO: 19901 GO: 8270 miR-372 AEBP2 Hs.126497 3 miR-372 AMPD2 Hs.82927 3 Purine metabolism miR-372 ANK2 Hs.567235 3 Ribosomal Proteins miR-372 APBB2 Hs.479602 3 GO: 30048 GO: 1540 GO: 30426 GO: 7409 GO: 35035 GO: 30027 GO: 7050 GO: 8134 GO: 16020 GO: 7242 GO: 5634 GO: 45749 GO: 45202 GO: 30308 GO: 50821 miR-372 APP Hs.434980 3 Alzheimer's disease GO: 7219 GO: 5507 GO: 9986 05010; GO: 6915 GO: 8201 GO: 5905 Neurodegenerative GO: 7155 GO: 5506 GO: 5576 Disorders 01510; GO: 6878 GO: 46872 GO: 5887 Hemostasis 109582 GO: 6897 GO: 5515 GO: 50905 GO: 4867 GO: 8270 miR-372 ARHGAP9 Hs.437126 3 GO: 5096 miR-372 ARHGEF10 Hs.98594 3 miR-372 ARID4A Hs.161000 3 GO: 6333 GO: 3682 GO: 785 GO: 45892 GO: 5515 GO: 5634 GO: 6350 GO: 3700 GO: 17053 GO: 6366 GO: 16564 miR-372 ARID4B Hs.533633 3 GO: 3677 GO: 5622 GO: 3676 miR-372 ATP2B2 Hs.268942 3 Calcium signaling GO: 6816 GO: 5524 GO: 16021 pathway 04020 GO: 6812 GO: 5509 GO: 5886 GO: 8152 GO: 5388 GO: 5516 GO: 16787 GO: 16820 miR-372 ATP2B4 Hs.343522 3 Calcium signaling GO: 6816 GO: 5524 GO: 5887 pathway 04020 GO: 6812 GO: 5509 GO: 5886 GO: 8152 GO: 5388 GO: 5516 GO: 16787 GO: 16820 miR-372 BAHD1 Hs.22109 3 miR-372 BCL11A Hs.370549 3 GO: 30097 GO: 46872 GO: 5737 GO: 6355 GO: 3676 GO: 5634 GO: 6350 GO: 8270 miR-372 BRP44L Hs.172755 3 GO: 5554 miR-372 BTG1 Hs.255935 3 Circadian Exercise GO: 16477 GO: 19900 GO: 5737 GO: 30308 GO: 3712 GO: 5634 GO: 8285 GO: 45766 GO: 45603 GO: 43085 miR-372 C15orf17 Hs.367690 3 miR-372 C16orf28 Hs643536 3 GO: 16567 GO: 4842 GO: 151 GO: 8270 miR-372 CCND2 Hs.376071 3 Cell cycle 04110; Focal GO: 51301 GO: 5634 adhesion 04510; Jak- GO: 74 STAT signaling pathway 04630; Wnt signaling pathway 04310; Cell Cycle 69278 miR-372 CDC2L6 Hs.159118 3 miR-372 CFL2 Hs.180141 3 G13 Signaling Pathway miR-372 COL23A1 Hs.413494 3 miR-372 TNXB Hs.42853 3 G1 to S cell cycle; Smooth muscle contraction miR-372 CRIM1 Hs.332847 3 miR-372 CUL4A Hs.339735 3 miR-372 DAZAP2 Hs.369761 3 Circadian Exercise miR-372 DMTF1 Hs.558441 3 miR-372 E2F5 Hs.445758 3 Cell cycle 04110; TGF- GO: 74 GO: 6355 GO: 5515 GO: 5634 beta signaling pathway GO: 6350 GO: 3700 GO: 5667 04350; Cell Cycle 69278 miR-372 EIF2C1 Hs.22867 3 GO: 6412 GO: 5515 GO: 5850 GO: 6446 GO: 3743 miR-372 EPAS1 Hs.468410 3 GO: 1525 GO: 3705 GO: 5634 GO: 30154 GO: 35035 GO: 6355 GO: 5515 GO: 1666 GO: 4871 GO: 7165 GO: 3713 GO: 6366 miR-372 EPHA2 Hs.171596 3 Axon guidance 04360 GO: 7275 GO: 5524 GO: 5887 GO: 6468 GO: 5003 GO: 16020 GO: 7165 GO: 166 GO: 7169 GO: 4674 GO: 4872 GO: 16740 miR-372 ERBB4 Hs.390729 3 Calcium signaling GO: 8283 GO: 5524 GO: 5887 pathway 04020; Dorso- GO: 7275 GO: 5006 GO: 16020 ventral axis formation GO: 6468 GO: 166 04320 GO: 7169 GO: 5515 GO: 4872 GO: 16740 miR-372 FBXL11 Hs.124147 3 GO: 6355 GO: 3677 GO: 6512 GO: 46872 GO: 5515 GO: 8270 miR-372 Transcribed Hs.246781 3 locus miR-372 FNDC3A Hs.508010 3 ECM-receptor interaction 04512 miR-372 GCAT Hs.54609 3 Glycine, serine and GO: 6520 GO: 8415 GO: 5739 threonine metabolism GO: 9058 GO: 8890 00260 GO: 16874 GO: 16769 miR-372 GPR161 Hs.271809 3 GPCRDB Class A Rhodopsin-like2 miR-372 GPR6 Hs.46332 3 GPCRDB Class A GO: 7186 GO: 16526 GO: 5887 Rhodopsin-like GO: 7165 GO: 4872 GO: 1584 miR-372 HBP1 Hs.162032 3 GO: 16055 GO: 3677 GO: 5634 GO: 6355 GO: 6350 miR-372 HIC2 Hs.517434 3 GO: 45892 GO: 3677 GO: 5634 GO: 6350 GO: 46872 GO: 8022 GO: 8270 miR-372 HNRPH3 Hs.198158 3 miR-372 IRF2 Hs.374097 3 Apoptosis GO: 8283 GO: 3702 GO: 5634 GO: 6955 GO: 3700 GO: 122 GO: 6355 GO: 6350 miR-372 KCNMA1 Hs.568865 3 miR-372 KIF3B Hs.369670 3 miR-372 KLF12 Hs.373857 3 GO: 6357 GO: 46872 GO: 5634 GO: 6350 GO: 3714 GO: 3700 GO: 8270 miR-372 LATS2 Hs.78960 3 GO: 82 GO: 7049 GO: 5524 GO: 5634 GO: 51301 GO: 287 GO: 166 GO: 922 GO: 9755 GO: 4674 GO: 7067 GO: 4713 GO: 45736 GO: 16740 GO: 6468 miR-372 LOC641518 Hs.535760 3 TGF Beta Signaling Pathway miR-372 LEF1 Hs.555947 3 Adherens junction GO: 16055 GO: 3677 GO: 5634 04520; Wnt signaling GO: 6355 pathway 04310 GO: 6350 miR-372 LHX6 Hs.103137 3 GO: 7420 GO: 46872 GO: 5634 GO: 6355 GO: 3700 GO: 8270 miR-372 LUC7L2 Hs.530118 3 GO: 46872 GO: 8270 miR-372 MBNL2 Hs.125715 3 miR-372 MEF2C Hs.444409 3 MAPK signaling GO: 7517 GO: 3702 GO: 5634 pathway 04010 GO: 7399 GO: 3713 GO: 6355 GO: 3700 GO: 6350 GO: 6366 miR-372 MKRN1 Hs.490347 3 GO: 4 GO: 16567 GO: 46872 GO: 8372 GO: 5554 GO: 151 GO: 3676 GO: 5515 GO: 4842 GO: 8270 miR-372 MTMR3 Hs.474536 3 GO: 46839 GO: 16787 GO: 5737 GO: 6470 GO: 4437 GO: 5624 GO: 46872 GO: 4722 GO: 4725 GO: 8270 miR-372 NEK9 Hs.7200 3 GO: 7049 GO: 5524 GO: 51301 GO: 287 GO: 166 GO: 7067 GO: 4674 GO: 6468 GO: 16740 miR-372 NEUROD1 Hs.72981 3 GO: 30154 GO: 3677 GO: 5634 GO: 7399 GO: 3702 GO: 6355 miR-372 NPAS3 Hs.509113 3 GO: 6355 GO: 3677 GO: 5634 GO: 7165 GO: 4871 GO: 30528 miR-372 NR4A2 Hs.165258 3 Nuclear Receptors GO: 19735) GO: 4879 GO: 5634 GO: 6355 GO: 46872 GO: 7165 GO: 3707 GO: 6350 GO: 3700 GO: 8270 miR-372 NR4A3 Hs.279522 3 Hypertrophy model GO: 4 GO: 6355 GO: 5488 GO: 5634 GO: 6350 GO: 4879 GO: 46872 GO: 3707 GO: 4887 GO: 3700 GO: 8270 miR-372 OSBPL8 Hs.430849 3 GO: 6869 GO: 8202 miR-372 PAPOLA Hs.253726 3 mRNA processing miR-372 PCAF Hs.533055 3 miR-372 PCDHA4 Hs.199343 3 miR-372 PERQ1 Hs.414396 3 miR-372 PHF1 Hs.166204 3 GO: 6355 GO: 46872 GO: 5634 GO: 3676 GO: 5515 GO: 3700 GO: 8270 miR-372 PHF2 Hs.211441 3 GO: 6355 GO: 46872 GO: 5634 GO: 5515 GO: 3700 GO: 8270 miR-372 PLAG1 Hs.14968 3 GO: 46872 GO: 5634 GO: 3676 GO: 3700 GO: 8270 miR-372 PLAGL2 Hs.154104 3 GO: 6355 GO: 46872 GO: 5634 GO: 6350 GO: 3700 GO: 8270 miR-372 POLK Hs.135756 3 DNA polymerase 03030 GO: 6281 GO: 3677 GO: 5634 GO: 6260 GO: 3887 GO: 6280 GO: 287 GO: 16740 GO: 8270 miR-372 POLQ Hs.241517 3 Purine metabolism; Pyrimidine metabolism; DNA polymerase miR-372 PPP3CA Hs.435512 3 Amyotrophic lateral GO: 6470 GO: 5509 GO: 5955 sclerosis 05030; GO: 5516 GO: 5634 Apoptosis 04210; Axon GO: 16787 guidance 04360; B cell GO: 5506 receptor signaling GO: 4722 pathway 04662; Calcium GO: 8270 signaling pathway 04020; MAPK signaling pathway miR-372 PPP3CA Hs.535457 3 G Protein Signaling; Calcium signaling pathway miR-372 PPP6C Hs.495128 3 GO: 82 GO: 6470 GO: 16787 GO: 5506 GO: 30145 GO: 46872 GO: 4722 miR-372 PRDM4 Hs.506655 3 GO: 8283 GO: 3677 GO: 5634 GO: 6355 GO: 3702 GO: 7165 GO: 46872 GO: 6350 GO: 8270 GO: 6366 miR-372 PRRX1 Hs.283416 3 miR-372 PUM1 Hs.144795 3 GO: 6812 GO: 5509 GO: 16021 GO: 6936 GO: 15269 GO: 16020 GO: 7269 GO: 287 GO: 8076 GO: 6813 GO: 30955 GO: 7268 GO: 5515 GO: 5249 miR-372 RAB11A Hs.321541 3 miR-372 RAB6A Hs.503222 3 GO: 6888 GO: 5525 GO: 5795 GO: 15031 GO: 3924 GO: 7264 GO: 166 GO: 5515 miR-372 RAB6C Hs.535586 3 GO: 6886 GO: 5525 GO: 5622 GO: 42493 GO: 3924 GO: 7264 GO: 166 miR-372 RAB7 Hs.15738 3 GO: 6897 GO: 6886 GO: 7264 miR-372 RAB7B Hs.534612 3 GO: 6886 GO: 5525 GO: 5764 GO: 7264 GO: 166 miR-372 RABGAP1 Hs.271341 3 miR-372 RALGDS Hs.106185 3 GO: 7264 GO: 5085 GO: 8372 miR-372 RBL2 Hs.513609 3 Cell cycle 04110; TGF- GO: 7049 GO: 3677 GO: 5634 beta signaling pathway GO: 45786 GO: 5515 04350 GO: 6355 GO: 6350 miR-372 RBM17 Hs.498548 3 mRNA processing miR-372 RDBP Hs.423935 3 Gene Expression 74160; GO: 4 GO: 6355 GO: 3723 GO: 5634 Transcription 74159 GO: 6350 GO: 166 GO: 5515 miR-372 RGL1 Hs.497148 3 GO: 7264 GO: 8321 GO: 8372 GO: 5515 miR-372 RHOC Hs.514941 3 miR-372 RPS6KA1 Hs.149957 3 Ribosomal Proteins; GO: 6468 GO: 5524 Calcium signaling GO: 7165 GO: 166 pathway; GO: 4672 Phosphatidylinositol GO: 4674 signaling system GO: 4713 GO: 3735 GO: 16740 miR-372 RPS6KA5 Hs.510225 3 MAPK signaling GO: 7173 GO: 5524 GO: 5634 pathway 04010 GO: 16572 GO: 3824 GO: 6468 GO: 8237 GO: 7243 GO: 166 GO: 6508 GO: 5515 GO: 6355 GO: 4674 GO: 422 GO: 4713 GO: 16740 miR-372 RSBN1 Hs.486285 3 miR-372 RTN1 Hs.368626 3 GO: 30182 GO: 5554 GO: 5783 GO: 7165 GO: 4871 GO: 30176 GO: 16021 miR-372 RUNX1 Hs.149261 3 GO: 7275 GO: 5524 GO: 5634 GO: 45944 GO: 5515 GO: 6355 GO: 3700 GO: 6350 GO: 16563 miR-372 SAR1B Hs.432984 3 GO: 6888 GO: 5525 GO: 5795 GO: 6886 GO: 287 GO: 166 GO: 5783 GO: 7264 GO: 16020 miR-372 SART1 Hs.502883 3 GO: 5829 miR-372 SENP1 Hs.371957 3 GO: 6508 GO: 8234 GO: 5634 GO: 6512 GO: 4175 miR-372 SLC2A4 Hs.380691 3 Adipocytokine signaling GO: 5975 GO: 5355 GO: 9897 pathway 04920; Insulin GO: 8643 GO: 5515 GO: 5887 signaling pathway GO: 42593 GO: 5351 GO: 16020 04910; Type II diabetes GO: 15758 GO: 5215 GO: 5624 mellitus 04930; GO: 48471 Metabolism of sugars GO: 12506 71387 miR-372 SLITRK3 Hs.101745 3 GO: 16021 miR-372 STAT3 Hs.463059 3 Adipocytokine signaling GO: 7259 GO: 5509 GO: 5737 pathway 04920; Jak- GO: 6953 GO: 5062 GO: 5634 STAT signaling pathway GO: 6928 GO: 4871 04630 GO: 19221 GO: 3700 GO: 7242 GO: 8134 GO: 122 miR-372 SUV39H1 Hs.522639 3 Lysine degradation GO: 67 GO: 6333 GO: 8757 GO: 785 00310 GO: 16568 GO: 3682 GO: 794 GO: 46974 GO: 5634 GO: 18024 GO: 5515 GO: 167 miR-372 SUV420H1 Hs.503001 3 miR-372 TIPARP Hs.12813 3 miR-372 TP53INP2 Hs.516994 3 miR-372 TRPS1 Hs.253594 3 GO: 6607 GO: 46872 GO: 5634 GO: 6355 GO: 3700 GO: 1501 GO: 8270 GO: 6350 GO: 6366 miR-372 TRPV6 Hs.302740 3 miR-372 TUSC2 Hs.517981 3 miR-372 UBE2B Hs.385986 3 Ubiquitin mediated GO: 6281 GO: 16874 GO: 16020 proteolysis GO: 6512 GO: 8642 GO: 5634 GO: 4842 miR-372 VLDLR Hs.370422 3 GO: 8203 GO: 5509 GO: 5905 GO: 6897 GO: 5319 GO: 16021 GO: 6629 GO: 5041 GO: 16020 GO: 6869 GO: 4872 GO: 5624 GO: 7613 GO: 7399 GO: 7165 GO: 8202 miR-372 YWHAZ Hs.492407 3 Cell cycle 04110 GO: 19904 miR-372 ZBTB4 Hs.35096 3 miR-372 ZDHHC17 Hs.4014 3 GO: 42953 GO: 8415 GO: 5795 GO: 43123 GO: 46872 GO: 16021 GO: 5515 GO: 16020 GO: 19706 GO: 4871 GO: 16740 GO: 8270 miR-372 ZNF238 Hs.69997 3 GO: 7001) GO: 46872 GO: 228 GO: 122 GO: 3676 GO: 5634 GO: 6355 GO: 5515 GO: 6350 GO: 3704 GO: 6810 GO: 3700 GO: 8270 miR-372 ZNF385 Hs.505653 3 miR-372 ZNF532 Hs.529023 3 GO: 3677 GO: 5634 GO: 46872 GO: 8270 miR-372 PRDM8 Hs.373642 3 GO: 6355 GO: 3677 GO: 5634 GO: 6350 GO: 46872 GO: 3676 GO: 8270 miR-372 DDOST Hs.523145 3 N-Glycan biosynthesis GO: 18279 GO: 4579 GO: 5789 00510 GO: 16740 GO: 16021 miR-372 ZFP91 Hs.524920 3 miR-372 FBXL4 Hs.536850 3 GO: 6512 GO: 5634 GO: 6511 GO: 151 miR-221 PHF1 Hs.166204 5 GO: 6355 GO: 46872 GO: 5634 GO: 3676 GO: 5515 GO: 3700 GO: 8270 miR-221 PHF2 Hs.211441 5 GO: 6355 GO: 46872 GO: 5634 GO: 5515 GO: 3700 GO: 8270 miR-221 ATP1A4 Hs.367953 5 Calcium regulation in GO: 15991 GO: 5524 GO: 16020 cardiac cells GO: 6812 GO: 15662 GO: 5890 GO: 30641 GO: 3824 GO: 8152 GO: 16787 GO: 6813 GO: 16820 GO: 6814 GO: 287 GO: 30317 GO: 15077 GO: 166 GO: 30955 GO: 31402 GO: 5391 miR-221 ZNF385 Hs.505653 5 miR-221 TCF12 Hs.511504 5 GO: 7275 GO: 3677 GO: 5634 GO: 6955 GO: 3702 GO: 7517 GO: 30528 GO: 45449 GO: 6357 miR-221 MESDC1 Hs.513071 5 miR-221 KHDRBS2 Hs.519794 5 miR-221 C20orf23 Hs.101774 4 GO: 7242 GO: 5524 GO: 5874 GO: 7018 GO: 3777 GO: 5875 GO: 166 miR-221 SLC25A37 Hs.122514 4 miR-221 MAPK10 Hs.125503 4 Apoptosis; Apoptosis; G13 Signaling Pathway; Integrin-mediated cell adhesion; MAPK Cascade; Wnt signaling miR-221 ARF4 Hs.148330 4 Cholera - Infection GO: 6888 GO: 5525 GO: 5795 05110 GO: 6886 GO: 3924 GO: 7264 GO: 8047 GO: 166 miR-221 VAPB Hs.182625 4 GO: 6461 GO: 5554 GO: 5887 GO: 5198 miR-221 DMRT3 Hs.189174 4 miR-221 PCDHA6 Hs.199343 4 GO: 7155 GO: 5509 GO: 5887 GO: 7156 GO: 5515 GO: 16020 GO: 7399 miR-221 NLK Hs.208759 4 miR-221 FOS Hs.25647 4 B cell receptor signaling GO: 6306 GO: 3677 GO: 5634 pathway 04662; MAPK GO: 6954 GO: 3704 signaling pathway GO: 6357 04010; T cell receptor signaling pathway 04660; Toll-like receptor signaling pathway 04620 miR-221 DHDDS Hs.369385 4 N-Glycan biosynthesis GO: 8152 GO: 16740 00510 miR-221 ATP1A1 Hs.371889 4 GO: 15991 GO: 5524 GO: 16020 GO: 6812 GO: 15662 GO: 5624 GO: 30641 GO: 16787 GO: 5890 GO: 8152 GO: 16820 GO: 6813 GO: 287 GO: 6814 GO: 15077 GO: 30317 GO: 166 GO: 30955 GO: 5515 GO: 31402 GO: 5391 miR-221 MGC16179 Hs.371889 4 miR-221 ANKHD1 Hs.434219 4 miR-221 PAK1 Hs.435714 4 Integrin-mediated cell adhesion miR-221 IRX5 Hs.435730 4 GO: 6355 GO: 3700 GO: 5634 miR-221 PKN1 Hs.466044 4 G13 Signaling Pathway GO: 7257 GO: 5524 GO: 5622 GO: 6468 GO: 166 GO: 7165 GO: 5515 GO: 4674 GO: 4713 GO: 16740 miR-221 GPI Hs.466471 4 Glycolysis/ GO: 5975 GO: 5125 GO: 5615 Gluconeogenesis 00010; GO: 6094 GO: 4347 Pentose phosphate GO: 6096 GO: 8083 pathway 00030; Starch GO: 7599 GO: 16853 and sucrose metabolism GO: 6959 00500; Metabolism of GO: 7399 sugars 71387 miR-221 MAP3K10 Hs.466743 4 MAPK signaling GO: 7257 GO: 5524 pathway 04010 GO: 6917 GO: 4706 GO: 46777 GO: 166 GO: 7165 GO: 42803 GO: 4674 GO: 4713 GO: 16740 miR-221 ARID1A Hs.468972 4 GO: 30521 GO: 3677 GO: 16514 GO: 16568 GO: 5488 GO: 5622 GO: 48096 GO: 5515 GO: 5634 GO: 30520 GO: 16563 GO: 42766 GO: 6355 GO: 6350 miR-221 PDCD10 Hs.478150 4 GO: 6915 miR-221 PPP6C Hs.495128 4 GO: 82 GO: 6470 GO: 16787 GO: 5506 GO: 30145 GO: 46872 GO: 4722 miR-221 PLEKHC1 Hs.509343 4 GO: 30036 GO: 5515 GO: 5856 GO: 7155 GO: 1725 GO: 8360 miR-221 RBM24 Hs.519904 4 miR-221 MEIS1 Hs.526754 4 GO: 6355 GO: 3702 GO: 5634 GO: 3700 miR-221 HECTD2 Hs.535293 4 GO: 15671 GO: 20037 GO: 5622 GO: 6512 GO: 5344 GO: 4842 miR-221 GNAI2 Hs.77269 4 Axon guidance 04360; GO: 7186 GO: 5525 Gap junction 04540; GO: 7194 GO: 3924 Tight junction 04530 GO: 7584 GO: 166 GO: 7165 GO: 4871 miR-221 CDKN1C Hs.106070 3 Cell cycle 04110 GO: 80 GO: 7049 GO: 4861 GO: 5634 GO: 7050 GO: 5515 GO: 8285 GO: 79 miR-221 GARNL1 Hs.113150 3 GO: 5096 GO: 5634 miR-221 MIA3 Hs.118474 3 GO: 6096 GO: 166 GO: 4618 miR-221 ARNT Hs.131494 3 GO: 60 GO: 6355 GO: 5061 GO: 5634 GO: 7165 GO: 5515 GO: 4872 GO: 4871 GO: 3713 GO: 3700 GO: 16563 miR-221 ITGA6 Hs.133397 3 Integrin-mediated cell adhesion miR-221 GPRC5B Hs.148685 3 GPCRDB Class C GO: 7186 GO: 8067 GO: 16021 Metabotropic glutamate GO: 7165 GO: 4872 GO: 16020 pheromone GO: 7601 GO: 5118 miR-221 CDC2L6 Hs.159118 3 miR-221 EIF5A2 Hs.164144 3 miR-221 CD4 Hs.17483 3 Cell adhesion molecules GO: 30217 GO: 42289 GO: 42101 04514; Hematopoietic GO: 45058 GO: 15026 GO: 16021 cell lineage 04640; T cell GO: 7155 GO: 5515 GO: 5886 receptor signaling GO: 6955 GO: 4888 pathway 04660 GO: 45086 GO: 8270 GO: 7169 miR-221 GABRA1 Hs.175934 3 Neuroactive ligand- GO: 6821 GO: 4890 GO: 5887 receptor interaction GO: 7214 GO: 5230 GO: 45211 04080 GO: 6811 GO: 5216 GO: 30594 miR-221 C1QDC1 Hs.234355 3 miR-221 CDKN1B Hs.238990 3 Cell cycle 04110 GO: 7050 GO: 4861 GO: 5737 GO: 8285 GO: 79 GO: 5515 GO: 5634 GO: 5072 miR-221 TRPS1 Hs.253594 3 GO: 6607 GO: 46872 GO: 5634 GO: 6355 GO: 3700 GO: 1501 GO: 8270 GO: 6350 GO: 6366 miR-221 DNAJC14 Hs.253844 3 miR-221 PGGT1B Hs.254006 3 GO: 18348 GO: 4662 GO: 5953 GO: 46872 GO: 4659 GO: 16740 GO: 8270 miR-221 MYO1C Hs.286226 3 GO: 5524 GO: 16459 GO: 3779 GO: 16461 GO: 5516 GO: 3774 GO: 166 miR-221 SEC24B Hs.292472 3 GO: 6888 GO: 5515 GO: 30127 GO: 6886 GO: 5215 GO: 5795 GO: 16192 GO: 5783 GO: 16020 miR-221 RAB1A Hs.310645 3 GO: 6888 GO: 5525 GO: 5795 GO: 15031 GO: 166 GO: 5783 GO: 7264 miR-221 ASB7 Hs.31845 3 GO: 7242 miR-221 LOC145758 Hs.31845 3 miR-221 ZFHX1B Hs.34871 3 TGF Beta Signaling Pathway miR-221 HRB Hs.352962 3 GO: 6406 GO: 3677 GO: 5643 GO: 43087 GO: 3723 GO: 5634 GO: 6810 GO: 46872 GO: 5515 GO: 8270 miR-221 EXOC8 Hs.356198 3 miR-221 CTCF Hs.368367 3 GO: 45786 GO: 3702 GO: 5634 GO: 122 GO: 46872 GO: 45893 GO: 3676 GO: 6350 GO: 3714 GO: 3700 GO: 8270 miR-221 MYO1E Hs.370392 3 GO: 30048 GO: 5524 GO: 16459 GO: 42623 GO: 3779 GO: 5516 GO: 146 GO: 166 miR-221 PRDM2 Hs.371823 3 GO: 6355 GO: 46872 GO: 5634 GO: 3676 GO: 3700 GO: 8270 miR-221 APG7L Hs.373959 3 miR-221 ATG7 Hs.373959 3 miR-221 VGLL4 Hs.373959 3 GO: 6355 GO: 5634 GO: 6350 miR-221 IRF2 Hs.374097 3 Apoptosis GO: 8283 GO: 3702 GO: 5634 GO: 6955 GO: 3700 GO: 122 GO: 6355 GO: 6350 miR-221 DAPK1 Hs.380277 3 GO: 6915 GO: 5524 GO: 15629 GO: 8624 GO: 4685 GO: 6468 GO: 5516 GO: 7243 GO: 4684 GO: 7165 GO: 166 GO: 4674 GO: 16740 miR-221 BMF Hs.386140 3 Apoptosis 109581 GO: 6915 GO: 5515 GO: 16459 miR-221 PAIP2 Hs.396644 3 GO: 45947 GO: 5515 GO: 5737 GO: 6445 GO: 30371 miR-221 EIF3S1 Hs.404056 3 Gene Expression 74160; GO: 6412 GO: 5515 GO: 5852 Translation 72766 GO: 6446 GO: 3743 miR-221 OGT Hs.405410 3 Blood group glycolipid GO: 6493 GO: 8375 GO: 5829 biosynthesis-lactoseries GO: 7584 GO: 5488 GO: 5634 00601; Blood group GO: 7165 GO: 5515 glycolipid biosynthesis- GO: 16757 neolactoseries 00602; Fructose and mannose metabolism 00051; Ganglioside biosynthesis 00604; Globoside metabolism 00603; Glycerolipid metabolism 00561; Glycosphingolipid metabolism 00600; High-mannose type N- glycan biosynthesis 00513; N-Glycan biosynthesis 00510; O- Glycan biosynthesis 00512 miR-221 CPNE8 Hs.40910 3 miR-221 PBX3 Hs.428027 3 GO: 7387 GO: 5515 GO: 5634 GO: 9790 GO: 3700 GO: 30902 GO: 7388 GO: 6355 GO: 45898 miR-221 ZFPM2 Hs.431009 3 GO: 6357 GO: 3677 GO: 5634 GO: 6350 GO: 3702 GO: 46872 GO: 3714 GO: 8270 miR-221 ANKHD1 Hs.434219 3 Translation Factors miR-221 RIMS3 Hs.434924 3 GO: 6887 GO: 45202 GO: 6836 miR-221 ATXN1 Hs.434961 3 GO: 3723 GO: 5737 GO: 5634 miR-221 EPB41L1 Hs.437422 3 miR-221 POLH Hs.439153 3 GO: 3723 GO: 5737 GO: 5634 miR-221 HOXC10 Hs.44276 3 GO: 9653 GO: 3702 GO: 5634 GO: 8284 GO: 3700 GO: 6355 miR-221 Transcribed Hs.446484 3 locus miR-221 IQCK Hs.460217 3 miR-221 OSBPL7 Hs.463320 3 GO: 6869 GO: 3676 GO: 8202 miR-221 DOCK10 Hs.46578 3 GO: 5525 GO: 51020 GO: 5488 GO: 5085 GO: 4872 miR-221 MYO10 Hs.481720 3 GO: 7165 GO: 5524 GO: 5856 GO: 3779 GO: 16459 GO: 3774 GO: 166 miR-221 PAIP1 Hs.482038 3 Translation Factors GO: 48255 GO: 3723 GO: 5737 GO: 45946 GO: 5515 GO: 6413 GO: 8494 miR-221 PAIP1 Hs.482038 3 Translation Factors miR-221 MYLIP Hs.484738 3 Tryptophan metabolism GO: 6928 GO: 8092 GO: 5737 00380 GO: 7399 GO: 16874 GO: 5856 GO: 16567 GO: 46872 GO: 16020 GO: 4842 GO: 151 GO: 8270 miR-221 POGZ Hs.489873 3 GO: 7275 GO: 3677 GO: 5634 GO: 46872 GO: 3676 GO: 8270 miR-221 VDAC3 Hs.491597 3 Calcium signaling GO: 15853 GO: 15482 GO: 5887 pathway 04020 GO: 6820 GO: 8308 GO: 5741 GO: 5739 miR-221 PLS3 Hs.496622 3 GO: 3779 GO: 15629 GO: 5509 GO: 5515 miR-221 NAV1 Hs.497369 3 GO: 6306 GO: 5524 GO: 6810 GO: 3677 GO: 17111 GO: 166 miR-221 KCNK2 Hs.497745 3 GO: 6811 GO: 3824 GO: 16021 GO: 6813 GO: 5216 GO: 16020 GO: 15271 GO: 5267 GO: 30955 GO: 5244 miR-221 INA Hs.500916 3 miR-221 GALNTL4 Hs.501911 3 O-Glycan biosynthesis GO: 5509 GO: 5795 00512 GO: 30145 GO: 16021 GO: 4653 GO: 5529 GO: 16740 GO: 16757 miR-221 QKI Hs.510324 3 GO: 3676 miR-221 YWHAG Hs.520974 3 Cell cycle 04110 GO: 7010 GO: 3779 GO: 5737 GO: 43066 GO: 5159 GO: 6469 GO: 19904 GO: 7088 GO: 42803 GO: 45664 GO: 5080 GO: 9966 GO: 8426 GO: 48167 miR-221 ANGPTL2 Hs.521731 3 GO: 7275 GO: 5102 GO: 5615 miR-221 TP53BP2 Hs.523968 3 GO: 6915 GO: 74 GO: 5070 GO: 5737 GO: 7165 GO: 5515 miR-221 VASH1 Hs.525479 3 GO: 7049 GO: 7050 miR-221 PPARGC1A Hs.527078 3 Adipocytokine signaling GO: 8380 GO: 3677 GO: 5665 pathway 04920; Insulin GO: 30521 GO: 3723 GO: 5634 signaling pathway 04910 GO: 50873 GO: 16455 GO: 1678 GO: 50681 GO: 45333 GO: 30374 GO: 7586 GO: 166 GO: 19395 GO: 8134 GO: 6094 GO: 6397 GO: 7005 GO: 46321 GO: 45722 GO: 35066 GO: 45893 GO: 6461 GO: 50821 GO: 42594 GO: 1659 GO: 6350 GO: 6367 miR-221 SOCS3 Hs.527973 3 Adipocytokine signaling GO: 7259 GO: 4860 pathway 04920; Insulin GO: 6916 signaling pathway GO: 7242 04910; Jak-STAT GO: 9968 signaling pathway GO: 1558 04630; Type II diabetes mellitus 04930 miR-221 HIPK1 Hs.532363 3 GO: 6468 GO: 5524 GO: 5634 GO: 6355 GO: 16301 GO: 6350 GO: 166 GO: 5515 GO: 4674 GO: 16740 miR-221 GNB3 Hs.534315 3 Energy Metabolism GO: 7186 GO: 3924 GO: 5834 163685 GO: 8217 GO: 4871 GO: 7165 miR-221 TFR2 Hs.544932 3 GO: 6879 GO: 8233 GO: 5887 GO: 6826 GO: 4872 GO: 6508 GO: 4998 miR-221 SLC4A4 Hs.5462 3 GO: 6820 GO: 5452 GO: 16021 GO: 6810 GO: 8510 GO: 5887 GO: 16020 miR-221 MAGI1 Hs.567389 3 Dentatorubropallidoluysi GO: 7155 GO: 5524 GO: 5886 an atrophy 05050; Tight GO: 7166 GO: 16301 GO: 5923 junction 04530 GO: 6461 GO: 166 GO: 8022 GO: 16740 miR-221 PAIP1 Hs.567929 3 Translation Factors miR-221 ADAM11 Hs.6088 3 GO: 7229 GO: 5178 GO: 16021 GO: 6508 GO: 4222 GO: 5886 miR-221 RALA Hs.6906 3 GO: 6935 GO: 5525 GO: 6886 GO: 166 GO: 7165 GO: 5515 GO: 7264 miR-221 PSMD8 Hs.78466 3 Proteasome 03050; Cell GO: 6508 GO: 74 GO: 5829 Cycle 69278; Cell Cycle GO: 5838) Checkpoints 69620; DNA Replication 69306 miR-221 ANGPTL4 Hs.9613 3 GO: 1525 GO: 4857 GO: 5576 GO: 30154 GO: 9267 GO: 43066 GO: 51005 GO: 45766 GO: 45834 GO: 1666 miR-221 FAM13A1 Hs.97270 3 miR-221 NTF3 Hs.99171 3 MAPK signaling GO: 6916 GO: 8083 pathway 04010 GO: 6928 GO: 7267 GO: 7399 GO: 7165 miR-221 RSBN1L Hs592289 3 miR-137 SON Hs.517262 5 GO: 6916 GO: 3677 GO: 8372 GO: 3725 GO: 5622 GO: 3676 GO: 5634 miR-137 ARID4B Hs.533633 4 GO: 3677 GO: 5622 GO: 3676 miR-137 CA7 Hs.37014 4 Nitrogen metabolism GO: 6730 GO: 4089 00910 GO: 16829 GO: 46872 GO: 8270 miR-137 CADPS Hs.127013 4 GO: 6887 GO: 5829 miR-137 CLPX Hs.113823 4 GO: 6457 GO: 5524 GO: 5739 GO: 15031 GO: 42623 GO: 46872 GO: 166 GO: 51082 GO: 8270 miR-137 COCH Hs.21016 4 GO: 7605 miR-137 CPNE8 Hs.40910 4 miR-137 CPSF6 Hs.369606 4 GO: 6397 GO: 3723 GO: 5634 GO: 166 miR-137 DHX40 Hs.29403 4 miR-137 DUSP4 Hs.417962 4 MAPK signaling GO: 165 GO: 17017 GO: 5634 pathway 04010 GO: 6470 GO: 74 GO: 16787 GO: 4725 GO: 8330 miR-137 EPHA7 Hs.73962 4 Axon guidance 04360 GO: 6468 GO: 5524 GO: 16021 GO: 7169 GO: 5003 GO: 16020 GO: 166 GO: 5515 GO: 4872 GO: 16740 miR-137 ESRRA Hs.110849 4 Nuclear Receptors GO: 6355 GO: 46872 GO: 5634 GO: 6350 GO: 5496 GO: 3707 GO: 3700 GO: 8270 miR-137 FKBP4 Hs.524183 4 Calcium signaling GO: 6457 GO: 5528 GO: 5737 pathway GO: 16853 GO: 5634 GO: 3755 GO: 30674 miR-137 FURIN Hs.513153 4 Notch Signaling GO: 7267 GO: 5509 GO: 5794 Pathway 157118; Post- GO: 6508 GO: 4276 GO: 16021 translational GO: 8233 GO: 30140 modification of proteins GO: 4289 163841 miR-137 HLF Hs.196952 4 GO: 7275 GO: 3690 GO: 5634 GO: 6355 GO: 48511 GO: 6350 GO: 6366 miR-137 HMGN3 Hs.77558 4 GO: 4 GO: 3677 GO: 785 GO: 46966 GO: 5634 miR-137 INPP5A Hs.523360 4 Inositol phosphate GO: 7154 GO: 16787 GO: 16020 metabolism 00562; GO: 4437 Phosphatidylinositol GO: 4445 signaling system 04070 miR-137 NMNAT3 Hs.208673 4 miR-137 NY-SAR- Hs.348418 4 41 miR-137 PPP3CB Hs.500067 4 Apoptosis 04210; Axon GO: 6470 GO: 74 GO: 5509 GO: 5955 guidance 04360; B cell GO: 7165 GO: 5516 receptor signaling GO: 6351 GO: 16787 pathway 04662; Calcium GO: 5506 signaling pathway GO: 4722 04020; MAPK signaling GO: 8270 pathway 04010; Natural killer cell mediated cytotoxicity 04650; T cell receptor signaling pathway 04660; Wnt signaling pathway 04310 miR-137 PTPN2 Hs.123352 4 Calcium signaling GO: 6470 GO: 16787 pathway; Type I GO: 4725 diabetes mellitus GO: 4872 miR-137 SYT1 Hs.310545 4 miR-137 TDRD7 Hs.193842 4 miR-137 WIF1 Hs.284122 4 Wnt signaling pathway GO: 16055 GO: 4713 04310 GO: 7267 GO: 7275 GO: 7165 miR-137 ZC3H6 Hs.190477 4 miR-137 ABHD6 Hs.476454 3 GO: 6725 GO: 16787 miR-137 ACSL6 Hs.14945 3 Adipocytokine signaling GO: 6637 GO: 16874 GO: 16021 pathway 04920; Fatty GO: 6629 GO: 4467 GO: 5792 acid metabolism 00071 GO: 8152 GO: 287 GO: 5741 GO: 5778 GO: 5886 miR-137 ACVR1 Hs.470316 3 Cytokine-cytokine GO: 6468 GO: 5524 GO: 5887 receptor interaction GO: 7178 GO: 287 GO: 16020 04060; TGF-beta GO: 30145 signaling pathway 04350 GO: 166 GO: 4713 GO: 4872 GO: 16740 GO: 5024 miR-137 AP3S1 Hs.406191 3 GO: 8286 GO: 5215 GO: 5795 GO: 6886 GO: 30125 GO: 6810 GO: 30119 GO: 30133 miR-137 ATBF1 Hs.569686 3 miR-137 ATP1B1 Hs.291196 3 Calcium regulation in GO: 6813 GO: 30955 GO: 16021 cardiac cells; Purine GO: 6814 GO: 31402 GO: 16020 metabolism GO: 6810 GO: 5391 GO: 5890 miR-137 ATXN1 Hs.434961 3 miR-137 POLH Hs.439153 3 GO: 3723 GO: 5737 GO: 5634 miR-137 BACH2 Hs.269764 3 GO: 6355 GO: 3677 GO: 5634 GO: 6350 GO: 5515 miR-137 C5orf13 Hs.483067 3 miR-137 CABLES2 Hs.301040 3 miR-137 CACNA1G Hs.194746 3 Calcium signaling GO: 6816 GO: 5509 GO: 16021 pathway 04020; Type II GO: 6812 GO: 5261 GO: 16020 diabetes mellitus 04930 GO: 8332 GO: 5624 GO: 5245 GO: 5891 miR-137 CHES1 Hs.434286 3 GO: 77 GO: 85 GO: 5515 GO: 5634 GO: 6355 GO: 3700 GO: 6350 miR-137 CHST9 Hs.567604 3 Cysteine metabolism GO: 5975 GO: 1537 GO: 5795 00272 GO: 7417 GO: 16740 GO: 16021 GO: 30203 GO: 31228 GO: 42446 GO: 6790 miR-137 CRSP2 Hs.407604 3 GO: 30521 GO: 16455 GO: 119 GO: 45944 GO: 30374 GO: 5634 GO: 6350 GO: 4872 GO: 6367 GO: 46966 GO: 42809 miR-137 CSDA Hs.221889 3 Tight junction 04530 GO: 122 GO: 3677 GO: 5737 GO: 6355 GO: 3702 GO: 5634 GO: 9409 GO: 3690 GO: 6350 GO: 3714 GO: 3700 miR-137 CSE1L Hs.90073 3 GO: 6915 GO: 5488 GO: 5737 GO: 8283 GO: 59 GO: 8262 GO: 5643 GO: 15031 GO: 8565 GO: 5634 miR-137 CUL3 Hs.372286 3 Ubiquitin mediated GO: 82 GO: 7049 GO: 5515 GO: 5634 proteolysis 04120 GO: 7050 GO: 8629 GO: 8284 GO: 6512 miR-137 DCDC2 Hs.512603 3 GO: 6968 GO: 7242 GO: 1764 miR-137 DMRT2 Hs.59506 3 GO: 8584 GO: 46872 GO: 5634 GO: 6355 GO: 3700 GO: 7530 GO: 8270 GO: 7548 GO: 6350 miR-137 DUSP8 Hs.41688 3 MAPK signaling GO: 188 GO: 17017 GO: 5737 pathway 04010 GO: 6470 GO: 16787 GO: 5634 GO: 4725 miR-137 DYRK1A Hs.368240 3 Benzoate degradation via GO: 7399 GO: 5524 GO: 5634 CoA ligation 00632; GO: 18108 GO: 4715 Inositol phosphate GO: 166 metabolism 00562; GO: 4674 Nicotinate and GO: 16740 nicotinamide metabolism 00760; Phosphatidylinositol signaling system 04070 miR-137 EIF2C1 Hs.22867 3 GO: 6412 GO: 5515 GO: 5850 GO: 6446 GO: 3743 miR-137 ENC1 Hs.104925 3 GO: 7275 GO: 3779 GO: 5856 GO: 7399 GO: 5515 GO: 5634 miR-137 EPAS1 Hs.468410 3 GO: 1525 GO: 3705 GO: 5634 GO: 30154 GO: 35035 GO: 6355 GO: 5515 GO: 1666 GO: 4871 GO: 7165 GO: 3713 GO: 6366 miR-137 EPHA4 Hs.371218 3 Axon guidance 04360 GO: 6468 GO: 5524 GO: 5887 GO: 7165 GO: 5003 GO: 16020 GO: 7169 GO: 166 GO: 4674 GO: 4872 GO: 16740 miR-137 ERG Hs.473819 3 GO: 8283 GO: 5515 GO: 5634 GO: 7275 GO: 4871 GO: 6468 GO: 3700 GO: 6355 GO: 7165 GO: 6350 miR-137 ESRRG Hs.444225 3 GO: 7275 GO: 50682 GO: 5634 GO: 45893 GO: 5516 GO: 6350 GO: 46872 GO: 5496 GO: 3707 GO: 3700 GO: 16563 GO: 8270 miR-137 FAM77C Hs.470259 3 miR-137 GABRA1 Hs.175934 3 Neuroactive ligand- GO: 6821 GO: 4890 GO: 5887 receptor interaction GO: 7214 GO: 5230 GO: 45211 04080 GO: 6811 GO: 5216 GO: 30594 miR-137 GPR85 Hs.152009 3 GPCRDB Class A GO: 7186 GO: 4872 GO: 16021 Rhodopsin-like GO: 7165 GO: 1584 miR-137 GPR88 Hs.170053 3 GPCRDB Other GO: 7186 GO: 16526 GO: 8372 GO: 7165 GO: 4872 GO: 16021 GO: 1584 miR-137 IFT20 Hs.4187 3 GO: 19861 miR-137 ITPR3 Hs.93235 3 Calcium regulation in cardiac cells; Smooth muscle contraction miR-137 KIAA2010 Hs.533887 3 GO: 15986 GO: 5488 GO: 5737 GO: 6817 GO: 46933 GO: 16020 GO: 46961 GO: 16469 miR-137 LGR4 Hs.502176 3 GO: 7186 GO: 16500 GO: 16021 GO: 7165 GO: 4872 miR-137 LRRN3 Hs.3781 3 miR-137 MITF Hs.166017 3 GO: 7275 GO: 3677 GO: 5634 GO: 30318 GO: 16563 GO: 6355 GO: 7605 miR-137 MTPN Hs.43297 3 miR-137 MYBPC1 Hs.567306 3 Striated muscle contraction miR-137 NAB2 Hs.159223 3 GO: 8283 GO: 3714 GO: 5634 GO: 16481 GO: 7399 GO: 6355 GO: 6350 miR-137 NRP1 Hs.131704 3 Axon guidance 04360 GO: 1525 GO: 4872 GO: 16021 GO: 7411 GO: 5021 GO: 16020 GO: 7155 GO: 5624 GO: 30154 GO: 7267 GO: 7399 GO: 9887 GO: 8284 GO: 7165 miR-137 OXSR1 Hs.475970 3 Calcium signaling GO: 6468 GO: 5524 pathway; GO: 7243 GO: 287 GO: 166 Phosphatidylinositol GO: 6979 GO: 5515 signaling system GO: 4674 GO: 4713 GO: 16740 miR-137 PDLIM3 Hs.85862 3 GO: 46872 GO: 5515 GO: 8270 miR-137 PHF15 Hs.483419 3 GO: 6355 GO: 5515 GO: 8270 miR-137 PITPNA Hs.429819 3 GO: 6629 GO: 8289 GO: 5622 GO: 6810 GO: 8525 GO: 7601 GO: 8526 miR-137 PLEKHA5 Hs.188614 3 GO: 4 GO: 5545 GO: 8372 miR-137 PPM1E Hs.245044 3 ; Calcium signaling pathway miR-137 PTGFRN Hs.418093 3 miR-137 RANBP2 Hs.199561 3 GO: 46907 GO: 8536 GO: 5643 GO: 6457 GO: 5488 GO: 5634 GO: 6606 GO: 16853 GO: 46872 GO: 3755 GO: 8270 miR-137 RBM12 Hs.246413 3 miR-137 RPS13 Hs.446588 3 Ribosome 03010; Gene GO: 6412 GO: 3735 GO: 5840 Expression 74160; Translation 72766 miR-137 RWDD4A Hs.133337 3 miR-137 SGCG Hs.37167 3 GO: 7010 GO: 5856 GO: 7517 GO: 16021 GO: 5886 GO: 16012 miR-137 SH3BP5 Hs.257761 3 GO: 7242 GO: 17124 GO: 5739 GO: 5070 GO: 5515 GO: 4860 miR-137 SIPA1L2 Hs.268774 3 GO: 5096 GO: 5515 miR-137 SLC17A6 Hs.242821 3 miR-137 SLC25A5 Hs.522767 3 Calcium signaling GO: 6839 GO: 15207 GO: 5887 pathway 04020; GO: 6810 GO: 5488 GO: 5743 Nucleotide metabolism GO: 5215 GO: 5739 15869 miR-137 SLC43A2 Hs.160550 3 miR-137 SLC6A15 Hs.44424 3 GO: 6836 GO: 5328 GO: 5887 GO: 15293 GO: 16020 miR-137 SLC7A9 Hs.408567 3 GO: 6520 GO: 15184 GO: 5887 GO: 6865 GO: 5279 GO: 5886 GO: 6461 GO: 6810 miR-137 SNX25 Hs.369091 3 GO: 7242 GO: 4871 miR-137 SRPK1 Hs.443861 3 mRNA processing GO: 30154 GO: 5524 GO: 5737 GO: 7059 GO: 287 GO: 166 GO: 5634 GO: 398 GO: 5515 GO: 6468 GO: 4674 GO: 7243 GO: 16740 GO: 50684 miR-137 ST18 Hs.147170 3 GO: 6355 GO: 3700 GO: 5634 miR-137 STX16 Hs.307913 3 SNARE interactions in GO: 6891 GO: 8565 GO: 5795 vesicular transport 04130 GO: 6886 GO: 5486 GO: 16021 GO: 16020 GO: 5792 miR-137 SV2A Hs.516153 3 ECM-receptor GO: 6810 GO: 15293 GO: 16021 interaction 04512 GO: 5215 GO: 16020 miR-137 TARDBP Hs.300624 3 GO: 7067 GO: 3723 GO: 5634 GO: 398 GO: 8017 GO: 6355 GO: 166 GO: 6350 GO: 5515 GO: 6366 GO: 3700 miR-137 TBC1D19 Hs.567531 3 GO: 5096 miR-137 TCF12 Hs.511504 3 miR-137 THBS4 Hs.211426 3 Cell Communication GO: 7155 GO: 5509 GO: 5578) 01430; ECM-receptor GO: 6930 GO: 8201 interaction 04512; Focal GO: 5515 adhesion 04510; TGF- GO: 5198 beta signaling pathway 04350; Hemostasis 109582 miR-137 THRAP1 Hs.282678 3 GO: 30521 GO: 16455 GO: 119 GO: 45944 GO: 30374 GO: 5634 GO: 6355 GO: 4872 GO: 6350 GO: 46966 GO: 6367 GO: 42809 miR-137 TRPS1 Hs.253594 3 GO: 6607 GO: 46872 GO: 5634 GO: 6355 GO: 3700 GO: 1501 GO: 8270 GO: 6350 GO: 6366 miR-137 TSSK3 Hs.512763 3 GO: 30154 GO: 5524 GO: 5622 GO: 7242 GO: 166 GO: 6468 GO: 4674 GO: 48240 GO: 4713 GO: 7283 GO: 16740 miR-137 UGP2 Hs.516217 3 Galactose metabolism GO: 6011 GO: 3983 00052; Nucleotide GO: 8152 GO: 16301 sugars metabolism GO: 16740 00520; Pentose and glucuronate interconversions 00040; Starch and sucrose metabolism 00500; Metabolism of sugars 71387 *Predicted by at least three of five algorithms (PicTar, TargetScan, Miranda, MirBase, and CRSD) ^(†)Analyzed according to KEGG (http://www.genome.jp/kegg/), GenMAPP (http://www..org/), and Reactome (http://www.reactome.org/)

TABLE 7 Predicted Pathways Affected By The microRNAs No. Predicted Pathway* microRNA Targets^(†) P value^(†) MAPK signaling pathway hsa-let-7a 55 9.0E−24 hsa-miR-372 22 5.5E−06 hsa-miR-182* 9 3.0E−05 hsa-miR-221 15 4.1E−04 hsa-miR-137 13 1.7E−03 Adipocytokine signaling hsa-miR-182* 6 2.7E−06 pathway hsa-miR-221 9 8.6E−06 hsa-miR-137 6 1.5E−03 hsa-miR-372 7 2.3E−03 hsa-let-7a 6 4.2E−02 VEGF signaling pathway hsa-miR-372 11 5.2E−06 hsa-miR-182* 5 7.0E−05 hsa-let-7a 9 2.0E−03 hsa-miR-137 4 4.6E−02 Wnt signaling pathway hsa-miR-372 22 4.3E−10 hsa-let-7a 21 8.3E−07 hsa-miR-182* 6 3.2E−04 hsa-miR-221 8 1.4E−02 Type II diabetes mellitus hsa-miR-221 6 2.6E−04 hsa-miR-137 5 1.3E−03 hsa-let-7a 7 1.5E−03 hsa-miR-182* 3 2.2E−03 Focal adhesion hsa-let-7a 37 3.2E−13 hsa-miR-182* 5 1.1E−02 hsa-miR-221 10 1.8E−02 Adherens junction hsa-let-7a 16 1.3E−05 hsa-miR-221 6 3.1E−02 hsa-miR-372 7 4.0E−02 Axon guidance hsa-miR-137 20 3.1E−12 hsa-let-7a 26 6.2E−11 hsa-miR-372 19 1.4E−08 B cell receptor signaling hsa-miR-372 11 9.6E−07 pathway hsa-let-7a 12 4.5E−06 hsa-miR-137 4 2.7E−02 Calcium signaling pathway hsa-miR-372 22 1.0E−08 hsa-let-7a 25 7.6E−08 hsa-miR-137 11 7.5E−04 Cell cycle hsa-miR-372 17 3.5E−09 hsa-miR-221 9 2.4E−04 hsa-let-7a 9 1.7E−02 ECM-receptor interaction hsa-let-7a 27 6.0E−16 hsa-miR-372 9 1.1E−03 hsa-miR-182* 4 2.3E−03 Epithelial cell signaling in hsa-miR-221 7 6.1E−05 Helicobacter pylori infection hsa-miR-182* 4 2.0E−04 hsa-let-7a 5 3.9E−02 Insulin signaling pathway hsa-miR-221 9 1.6E−03 hsa-miR-182* 4 7.8E−03 hsa-let-7a 10 3.2E−02 Long-term potentiation hsa-miR-372 12 1.6E−06 hsa-let-7a 12 5.1E−05 hsa-miR-137 5 1.5E−02 *Listed only which are regulated by at least three of five microRNAs selected in this study ^(†)Analyzed by GeneSpring software (f) Kaplan-Meier Survival Analysis of a 3-microRNA Signature

Applying Kaplan-Meier survival analysis, a 3-microRNA signature, composed of hsa-miR221, hsa-miR372, and hsa-miR137, was also found to be associated with patients' post-treatment survival. As shown below, this result is statistically significant.

Training Dataset (n=56):

In overall survival analysis, P value=0.0013

In relapse-free survival analysis, P value=0.0437

Testing Dataset (n=56):

In overall survival analysis, P value=0.1468

In relapse-free survival analysis, P value=0.0841

Independent Cohort (n=62):

In overall survival analysis, P value=0.0359

In relapse-free survival analysis, P value=0.0985

Training Dataset and Testing Dataset (n=112):

In overall survival, P value=0.0011

In relapse-free survival, P value=0.0119

The P values were obtained from log-rank test for testing different survival curves between high and low risk groups of patients.

Other Embodiments

All of the features disclosed in this specification may be combined in any combination. Each feature disclosed in this specification may be replaced by an alternative feature serving the same, equivalent, or similar purpose. Thus, unless expressly stated otherwise, each feature disclosed is only an example of a generic series of equivalent or similar features.

From the above description, one skilled in the art can easily ascertain the essential characteristics of the present invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. For example, compounds structurally analogous to oxadiazole compounds described above also can be made, screened for the above-described activities and used to practice this invention. Thus, other embodiments are also within the claims. 

1. A method of predicting post-treatment survival of a lung cancer patient, comprising detecting expression levels of microRNAs hsa-miR137, hsa-miR372, hsa-miR182*, hsa-miR221, and hsa-let-7a in a lung cancer patient who has been subjected to treatment; calculating a risk score of the patient based on the expression levels of these microRNAs; and determining prospect of post-treatment survival based on the value of the risk score.
 2. The method of claim 1, wherein the risk score is calculated as follows: (0.15×expression level of hsa-miR137)+(0.31×expression level of hsa-miR372)+(0.28×expression level of hsa-miR182*)+(−0.13×expression level of hsa-miR221)+(−0.14×expression level of hsa-let-7a).
 3. The method of claim 2, wherein a risk score equal to or lower than −7.1 indicates that the patient has a fair prospect of post-treatment survival.
 4. The method of claim 1, wherein the patient has non-small cell lung cancer.
 5. The method of claim 4, wherein the patient is in stage I, II, or III of the non-small cell lung cancer.
 6. The method of claim 1, wherein the patient has been subjected to surgical treatment, chemical treatment, radio-therapy, or a combination thereof. 